Podcasts about krd

In this JCO Article Insights episode, Michael Hughes summarizes “International Myeloma Society and International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma" by Avet-Loiseau et al. published on June 09, 2025 along with an interview with author Dr Nikhil C. Munshi, MD. TRANSCRIPT Michael Hughes: Welcome to this episode of JCO Article Insights. This is Michael Hughes, JCO's editorial fellow. Today I am interviewing Dr. Nikhil Munshi on the “International Myeloma Society and International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma” by Avet-Loiseau et al. At the time of this recording, our guest has disclosures that will be linked in the transcript. While some patients with multiple myeloma live for decades after treatment, others exhibit refractory or rapidly relapsing disease irrespective of treatment administered. We term this “high-risk myeloma.” Multiple risk stratification systems have been created, starting with the Durie-Salmon system in 1975 and evolving with the advent of novel therapeutics and novel treatment approaches. In 2015, the Revised International Staging System (R-ISS) was introduced, which incorporated novel clinical and cytogenetic markers and remained, until recently, a mainstay of risk stratification in newly diagnosed disease. Myeloma as a field has, just in the past few years, though, undergone explosive changes. In particular, we have seen groundbreaking advances not only in treatments - the introduction of anti-CD38 agents and the advent of cellular and bispecific therapies - but also in diagnostic technology and our understanding of the genetic lesions in myeloma. This has led to the proliferation of numerous trials employing different definitions of high-risk myeloma, a burgeoning problem for patients and providers alike, and has prompted attempts to consolidate definitions and terminology. Regarding cytogenetic lesions, at least, Kaiser et al's federated meta-analysis of 24 therapeutic trials, published here in the JCO in February of 2025 and recently podcasted in an interview with associate editor Dr. Suzanne Lentzsch, posited a new cytogenetic classification system to realize a shared platform upon which we might contextualize those trial results. This article we have here by Dr. Avet-Loiseau, Dr. Munshi, and colleagues, published online in early June of this year and hot off the presses, is the definitive joint statement from the International Myeloma Society (IMS) and the International Myeloma Working Group (IMWG). What is high-risk multiple myeloma for the modern era? The IMS and IMWG Genomics Workshop was held in July 2023 and was attended by international myeloma experts, collaborating to reach consensus based on large volumes of data presented and shared. The datasets included cohorts from the Intergroupe Francophone du Myélome (IFM); the HARMONY project, comprised of multiple European academic trials; the FORTE study, findings from which solidified KRd as a viable induction regimen; the Grupo Español de Mieloma Múltiple (GEM) and the PETHEMA Foundation; the German-Speaking Myeloma Multicenter Group (GMMG); the UK-based Myeloma XI, findings from which confirmed the concept of lenalidomide maintenance; Emory 1000, a large, real-world dataset from Emory University in Atlanta; the Multiple Myeloma Research Foundation Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) dataset; and some newly diagnosed myeloma cohorts from the Mayo Clinic. Data were not pooled for analyses and were assessed individually - that is to say, with clear a priori understanding of whence the data had been gathered and for what original purposes. Consensus on topics was developed based on the preponderance of data across studies and cohorts. In terms of results, substantial revisions were made to the genomic staging of high-risk multiple myeloma, and these can be sorted into three major categories: A) alterations to the tumor suppressor gene TP53; B) translocations involving chromosome 14: t(14;16) (c-MAF overexpression), t(14;20) (MAFB overexpression), and t(4;14) (NSD2 overexpression); and C) chromosome 1 abnormalities: deletions of 1p or additional copies of 1q. In terms of category A, TP53 alterations: Deletion of 17p is present in up to 10% of patients at diagnosis and is enriched in relapsed or refractory disease. This is well-documented as a high-risk feature, but the proportion of the myeloma cells with deletion 17p actually impacts prognosis. GEM and HARMONY data analyses confirmed the use of 20% clonal cell fraction as the optimal threshold value for high-risk disease. That is to say, there must be the deletion of 17p in at least 20% of the myeloma cells on a FISH-analysis of a CD138-enriched bone marrow sample to qualify as high-risk disease. TP53 mutations can also occur. Inactivating mutations appear to have deleterious effects similar to chromosomal losses, and the biallelic loss of TP53, however it occurs, portends particularly poor prognosis. This effect is seen across Myeloma XI, CoMMpass, and IFM cohorts. Biallelic loss is rare, it appears to occur in only about 5% of patients, but next-generation sequencing is nevertheless recommended in all myeloma patients. Category B, chromosome 14 translocations: Translocation t(14;16) occurs in about 2% to 3% of patients with newly diagnosed disease. In the available data, primarily real-world IFM data, t(14;16) almost always occurs with chromosome 1 abnormalities. Translocation t(4;14) occurs in about 10% to 12% of newly diagnosed disease, but only patients with specific NSD2 alterations are, in fact, at risk of worse prognosis, which clinically appears to be about one in every three of those patients. And so together, the CoMMpass and Myeloma XI data suggest that translocation t(4;14) only in combination with deletion 1p or gain or amplification of 1q correlates with worse prognosis. Translocation t(14;20) occurs in only 2% of newly diagnosed disease. Similar to translocation t(4;14), it doesn't appear to have an effect on prognosis, except if the translocation co-occurs with chromosome 1 lesions, in which case patients do fare worse. Overall, these three translocations - t(14;16), t(4;14), and t(14;20) - should be considered high-risk only if chromosome 1 aberrations are also present. In terms of those chromosome 1 aberrations, category C, first deletions of 1p: Occurring in about 13% to 15% of newly diagnosed disease, deletion 1p eliminates critical cell checkpoints and normal apoptotic signaling. In the IFM and CoMMpass dataset analyses, biallelic deletion of 1p and monoallelic deletion of 1p co-occurring with additional copies of 1q denote high-risk. In terms of the other aberration in chromosome 1 possible in myeloma, gain or amplification of 1q: This occurs in up to 35% to 37% of newly diagnosed disease. It upregulates CKS1B, which is a cyclin-dependent kinase, and ANP32E, a histone acetyltransferase inhibitor. GEM and IFM data suggest that gain or amplification of 1q - there was no clear survival detriment to amplification - is best considered as a high-risk feature only in combination with the other risk factors as above. Now, in terms of any other criteria for high-risk disease, there remains one other item, and that has to do with tumor burden. There has been a consensus shift, really, in both the IMS and IMWG to attempt to develop a definition of high-risk disease which is based on biologic features rather than empirically observed and potentially temporally dynamic features, such as lactate dehydrogenase. Beta-2 microglobulin remains an independent high-risk indicator, but care must be taken when measuring it, as renal dysfunction can artificially inflate peripheral titers. The consensus conclusion was that a beta-2 microglobulin of at least 5.5 without renal failure should be considered high-risk but should not preclude detailed genomic profiling. So, in conclusion, the novel 2025 IMS-IMWG risk stratification system for myeloma is binary. It's either high-risk disease or standard-risk disease. It's got four criteria. Number one, deletion 17p and/or a TP53 mutation. Clonal cell fraction cut-off, remember, is 20%. Or number two, an IGH translocation - t(4;14), t(14;16), t(14;20) - with 1q gain and/or deletion of 1p. Or a monoallelic deletion of 1p with 1q additional copies or a biallelic deletion of 1p. Or a beta-2 microglobulin of at least 5.5 only when the creatinine is normal. This is a field-defining work that draws on analyses from across the world to put forward a dominant definition of high-risk disease and introduces a new era of biologically informed risk assessment in myeloma. Now, how does this change our clinical approach? FISH must be performed on CD138-enriched samples and should be performed for all patients. Next-generation sequencing should also be performed on all patients. Trials will hopefully now begin to include this novel definition of high-risk multiple myeloma. It does remain to be seen how data from novel therapeutic trials, if stratified according to this novel definition, will be interpreted. Will we find that therapies being evaluated at present have differential effects on myelomas with different genetic lesions? Other unanswered questions also exist. How do we go about integrating this into academic and then community clinical practice? How do we devise public health interventions for low-resource settings? To discuss this piece further, we welcome the esteemed Dr. Nikhil Munshi to the podcast. Dr. Munshi is a world-renowned leader in multiple myeloma and the corresponding author on this paper. As Professor of Medicine at Harvard Medical School, Director of the Multiple Myeloma Effector Cell Therapy Unit, and Director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center of the Dana-Farber Cancer Institute, he has presided over critical discoveries in the field.  Thank you for joining us, Dr. Munshi. Dr. Nikhil Munshi: Oh, it's my pleasure being here, Michael, to discuss this interesting and important publication. Michael Hughes: I had a few questions for you. So number one, this is a comprehensive, shall we say, monumental and wide-ranging definition for high-risk myeloma. How do you hope this will influence or impact the ways we discuss myeloma with patients in the exam room? And how do we make some of these components recommended, in particular next-generation sequencing, feasible in lower-resource settings? Dr. Nikhil Munshi: So those are two very important questions. Let's start with the first: How do we utilize this in our day-to-day patient care setting? So, as you know well, we have always tried to identify those patients who do not do so well with the current existing treatment. And for the last 30 years, what constitutes a myeloma of higher risk has continued to change with improvement in our treatment. The current definition basically centers around a quarter of the patients whose PFS is less than 2 to 3 years. And those would require some more involved therapeutic management. So that was a starting point of defining patients and the features. As we developed this consensus amongst ourselves - and it's titled as “International Myeloma Society, International Myeloma Working Group Consensus Recommendation” - this IMS-IMWG type of recommendation we have done for many years, improvising in various areas of myeloma care. Now, here, we looked at the data that was existing all across the globe, utilizing newer treatment and trying to identify that with these four-drug regimens, with transplant and some of the immunotherapy, which group of patients do not do as well. And this is where this current algorithm comes up. So before I answer your question straight, “How do we use it?” I might like to just suggest, “What are those features that we have identified?” There are four features which constitute high-risk disease in the newer definition. Those with deletion 17p with 20% clonality and/or TP53 mutation. Number two, patients with one of the translocations - t(4;14), t(14;16), or t(14;20) - co-occurring with 1q amplification or deletion 1p32. And that's a change. Previously, just the translocation was considered high-risk. Now we need a co-occurrence for it to be called high-risk. The third group is patients having biallelic deletion 1p32 or monoallelic deletion 1p32 along with 1q amplification. And finally, patients with high beta-2 microglobulin, more than or equal to 5.5 mg/dL, with normal creatinine less than 1.2 mg/dL. And the question, “How do we use this?” There are multiple areas where we incorporate high-risk features in our treatment algorithm. One of the first areas is where we would consider the induction regimen. If a patient has a high-risk disease, we would definitely consider a four-drug regimen rather than a three-drug regimen, although we are beginning to incorporate four-drug for all groups. That's one important thing. Number two, those are the patients where we do consider consolidation with transplant or maybe in the new world, considering some of the immunotherapeutic consolidation more early or more aggressively. Number three, these are the patients who get a little bit more maintenance therapy. So normally, lenalidomide might end up being our standard maintenance regimen. In patients who have high-risk disease, we incorporate either addition of daratumumab or the anti-CD38 targeting antibody and/or addition of proteasome inhibitor, either bortezomib or carfilzomib. So you would have multi-drug maintenance therapy in these patients. And in high-risk patients, we follow them with maintenance longer periods of time. One very critically important point to keep in mind is that to get the better outcome in high-risk disease, we must try to get them into MRD negativity because there is clear data that patients who do achieve MRD negativity, despite having high-risk disease, have a much superior outcome. They become near to standard-risk disease. And so, in high-risk patients, I would try to do whatever various options I have to try and get them into MRD-negative status. And when these patients relapse, we do not wait for the classic progression criteria to be met before we intervene. We would propose and suggest that we intervene earlier before the disease really blasts off. And so there are a number of areas in our setting where this high-risk definition will help us intervene appropriately and also with appropriate aggressiveness to achieve better outcome, to make this similar to standard-risk disease. Michael Hughes: Thank you, Dr. Munshi. And thoughts on how to really integrate this not only into academic centers but also lower-resource settings? Dr. Nikhil Munshi: So that's a very important question, Michael. And when we were developing this consensus, we were very cognizant of that fact. So wherever available, I think we are recommending that over a period of next 2, 3, 5 years, we should begin to switch over to sequencing-based methods because two components of this definition, one is TP53 mutation, which we cannot do without sequencing, and also reliably detecting deletion 1p requires sequencing-based method. So in the low-resource countries - and there are many in this world, and also even in our own country, patients may not be able to afford it - the older method with FISH or similar such technology, which is more affordable, is also acceptable for current time. They may miss a very small number of patients, maybe 2% to 3%, where these finer changes are not picked up, but a majority of this would be captured by them. So the current practice might still be applicable with some limitation in those patient populations, and that's what we would recommend. What is happening, fortunately, is that actually sequencing-based method is becoming cheaper. And in many centers, it is cheaper to do the sequencing rather than to do the FISH analysis. And so my hope is that even in low-resource centers, sequencing might be more economical in the end. It's, I think, the access to technology, which is a little bit limited currently, but it's hopefully becoming available soon. Michael Hughes: Thank you, Dr. Munshi. And staying for a minute and looking at the multiple myeloma subsets which might be missed by this really still very broad-ranging high-risk definition, at least by prior risk stratification systems, right, there is this group of patients who have standard-risk cytogenetics by R-ISS or R2-ISS, but they have primary refractory disease or they relapse early. We call these, as you are well aware, functionally high-risk disease. What proportion of previously FHR, functionally high-risk, myeloma patients do you expect to be captured by this novel definition? Dr. Nikhil Munshi: So I think the newer definition - and we can look at it both ways, but the newer definition should capture most of the functionally high-risk definition. To put it differently, Michael, there are patients who we know are, as you mentioned, functionally high-risk. Those are the patients who might have plasma cell leukemia, those who might have extramedullary disease, those who might not respond to our four-drug induction. If you don't respond to the four-drug induction, almost by definition, they are high-risk. However, a majority of them have one of the abnormalities that we are describing here. There would be a very small proportion which may not have. And if they do not have, we know one of the important components of this definition here is also that the genome, we know, keeps on evolving. So there may be a very small clone with the high-risk feature which was not obvious in the beginning. Following treatments or following relapse, that clone predominates, and now the patient's disease becomes high-risk.  So the definition would incorporate or would capture these functional high-risk patients, but as you said, in countries where resources are not available, using this functional high-risk would also be helpful and advantageous. Sometimes LDH ends up being a high-risk. In our studies, LDH has not come out to be high-risk anymore because the features we are describing captures most of those patients, but those alternatives, older, can still be considered if other newer techniques are not available. Michael Hughes: Got you. And in terms of these older definitions, yes, that incorporate tumor burden, these empirical observations about how myeloma presents, do you foresee any additional tumor burden indicators being added to future definitions of high-risk disease? Or do you instead see this particular definition as a major waypoint on the journey towards a fully biologically grounded definition of high-risk disease? Dr. Nikhil Munshi: I think your second part is what is going to happen. I think the tumor burden-related definition is being now replaced by the biological or genomic-based definition. And I think at some point, it will be quite fully replaced. One component not here, and it is because one thing, we don't have enough data; number two, we don't know how it will pan out, is also the influence of the microenvironment on the risk definition. For example, the immune system, the immune function, etc. But not enough data exists to suggest how it would change the current definition. So in future, would a definition be totally genomic or it could be more integrative? And my personal guess is that it would be more integrative and that some immune features might come into the picture, especially now that we are using immune-based therapy as a very important component of treatment - CAR T-cells, bispecific, and antibody-based treatments. What role the immune system plays in either supporting tumor or what role suppression of the anti-tumor immunity plays? They all will be important how patient outcomes end up being, and which in turn could translate into how patient's risk stratification might happen. So I think the older tumor burden-related definitions probably will become things of the past. What we have currently proposed and consensus developed is the new path forward, and over time, some microenvironmental influences, if defined and found to be important, may get some more incorporation if it compares favorably with the genomic features. Michael Hughes: Thank you, Dr. Munshi for that enlightening response.  To conclude the podcast, I'd like to look to the future and to the immediate future, what are the next steps for high-risk disease definition between now and discussing an integrated genomic-microenvironment-based definition? Will we see attempts to refine? Will we see a multi-level system, things like this? Dr. Nikhil Munshi: Yeah, so I think the current definition will be here to stay for the next 10 years or so. I think this has been developed using a large amount of data, so we do believe that this will remain fine. It has been validated now within the last six months by a few of the other studies. So there won't be a quick change. But we will try to, all of us will try to innovate. And as you very rightly bring up, the areas of research would include looking at the expression or transcriptomic component. Does that matter? And we do believe a small number of patients will have transcriptomic changes, not looked at the DNA changes, and may play a role. There are newer components, so long non-coding RNA, for example, is going to be an important component to look at, how it impacts the disease outcome, etc. There are also some of the proteomic-related changes which may become important in our studies. And then as we discussed, microenvironment and immunological changes. So these are the future areas of ongoing research where we all should collect data, and then in the next 5 to 10 years, we'll have another group meeting to see has anything changed or any of the features have become more important.  Most of the time, some of the older features are lost because they are not as critically high-risk, and the newer features come in. And so the historical background for just one second, there was a time when chromosome 13 was considered a high-risk disease. We now don't even mention it because it's not high-risk. The newer treatments have improved the outcome. t(4;14) used to be a high-risk disease. Now by itself today, in this definition by itself is not; it needs to be with something else. And so I think this is a great sign of progress. As we improve the treatment and outcomes, some of the features will become less important, new features will come up, and we'll need to keep on evolving with time and with technology and make it better for patients. Michael Hughes: Thank you so much, Dr. Munshi, for your wisdom, for your sagacity, for your historical perspective as well.  Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries. And be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

What a treat. Today we had Michael Demmer back on the show AND he was in person. If you haven't heard the first episode with him, please check out episode 181. We get into all sorts of great dog training conversations as we talk through SRS and field trials and raising dogs to be excellent. We then jump into some good Q&A from patreon friends and discuss the following: raising puppies to be great field trial dogs, building successful dogs, quality training vs quantity, corrections during popping, how dog training evolves, poison birds and KRD drills and when and how Michael prepares for The Grand and what his set ups are like. Check out our patreon to get 1:1 coaching, talk directly with Bob and join our happy hour hang outs. Need some training gear or want to support the Lone D? Check out our website for anything you need! Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode, we discuss the management of newly diagnosed transplant in-eligible multiple myeloma with Dr. Timothy Schmidt, with a special focus on IMROZ and BENEFIT RCTs testing quadruplets in this space. Here are the key papers we discussed: 1. MAIA trial (Daratumumab-Lenalidomide-Dexamethasone [DRd] vs Rd in newly diagnosed transplant ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/34655533/2. S0777 trial (VRd vs Rd in newly diagnosed myeloma [transplant-ineligible or transplant-deferred]): https://pubmed.ncbi.nlm.nih.gov/32393732/3. IMROZ trial (Isatuximab-VRd vs VRd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38832972/4. IFM-2020/BENEFIT trial (Isatuximab-VRd vs Isatuximab-Rd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38830994/5. GEM2017FIT trial (VMP-Rd vs KRd vs Dara-KRd in newly diagnosed transplant-ineligible myeloma): https://ashpublications.org/blood/article/142/Supplement%201/209/500199 

In this episode, we discuss the key abstracts in myeloma and related plasma cell disorders at ASH23 with Dr. Benjamin Derman. Here are the abstracts discussed in this episode: First, we will focus on a few abstracts in precursor states, MGUS. 1.      New diagnostic criteria for light chain MGUS (IStopMM):              https://ash.confex.com/ash/2023/webprogram/Paper188547.html             https://ash.confex.com/ash/2023/webprogram/Paper182661.html2.     PERSEUS Trial-Dara-VRD vs VRD in newly diagnosed transplant-eligible myeloma: https://ash.confex.com/ash/2023/webprogram/Paper191911.html 3.     ISKIA trial: Isa-KRD vs KRD in newly diagnosed transplant-eligible myeloma: https://ash.confex.com/ash/2023/webprogram/Paper177546.html 4.     Phase 1/2 study for Daratumumab-Venetoclax-Dexamethasone in early relapsed t(11;14) myeloma: https://ash.confex.com/ash/2023/webprogram/Paper180766.html 5.     GMMG Relapse Trial (Long-term follow-up data from randomized controlled trial of salvage transplant in myeloma) https://ash.confex.com/ash/2023/webprogram/Paper178835.html 6.     Overall survival results of KarMMa-3 trial https://ash.confex.com/ash/2023/webprogram/Paper178933.html 7.      GEM2017FIT Trial: Dara-KRd vs KRd vs VMP-RD in non-transplant eligible patients: https://ash.confex.com/ash/2023/webprogram/Paper179866.html      

Featuring an interview with Dr Joseph Mikhael, including the following topics: Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy for newly diagnosed multiple myeloma (MM) (0:00) KRd versus elotuzumab and KRd for transplant-eligible patients with newly diagnosed MM (10:47) Subgroup analysis of patients with 1q21 and other cytogenetic abnormalities in the Phase III IKEMA and ICARIA-MM studies (15:12) Results with ciltacabtagene autoleucel among patients with relapsed/refractory (R/R) MM in the CARTITUDE-1 study (26:59) CARTITUDE-4 study: Ciltacabtagene autoleucel in earlier lines of treatment for patients with lenalidomide-refractory MM (34:56) KarMMa-3 trial: Idecabtagene vicleucel for patients with R/R MM (44:20) GPRC5D-targeted CAR (chimeric antigen receptor) T-cell therapy for patients with R/R MM (49:09) Efficacy of teclistamab for R/R MM in the MajesTEC-1 trial (53:45) Efficacy of elranatamab for R/R MM in the MagnetisMM-3 trial (58:43) Efficacy of linvoseltamab for R/R MM in the LINKER-MM1 trial (1:02:01) Talquetamab for patients with R/R MM in the MonumenTAL-1 trial (1:04:16) Future directions in the first-line management of MM (1:06:03) Strategies to improve diversity and inclusion in clinical trials (1:10:53) CME information and select publications

In this episode, Mark Mirsky from KRD in Chicago shares his experiences in balancing work and his passion for coaching soccer, emphasizing the importance of work-life balance. He also reveals how his love for soccer led to unexpected connections, including a memorable trip to London to watch Manchester United play at Arsenal. Through their conversation, Mark highlights the significance of finding one's "and" beyond their profession, inspiring listeners to embrace their diverse identities and support one another's unique passions. Tune in to hear Mark's insightful perspectives on sports, work-life balance, and the power of sharing our stories.

König Peter vom Königreich Deutschland (KRD) war in letzter Zeit auf YouTube sehr präsent. Dazu kommen diverse Dokus im Mainstream. Ist das KRD wirklich ein echter Staat und sogar eine Alternative zur brd wo nicht einmal Steuern erhoben werden? In diesem Gespräch nimmt Frank Kraemer auch kritische Positionen auf, die über das KRD im Netz kursieren und zu denen König Peter Stellung bezieht. Hier ist der zweite von zwei Teilen. Einen aktuellen Überblick zu allen Kanälen findest Du hier:►  https://linktr.ee/frankkraemer Frank Kraemer im Gespräch findest Du auf folgenden Podcast-Plattformen:►  Spotify: https://open.spotify.com/show/1QDSCBerBukKvEMLFAjHoW►  Google Podcasts: https://www.google.com/podcasts?feed=aHR0cHM6Ly9hbmNob3IuZm0vcy80YjIzYzA1OC9wb2RjYXN0L3Jzcw==►  RadioPublic: https://radiopublic.com/d3b-podcast-6LBkjL►  Pocket Casts: https://pca.st/tg41uhyf►  Anchor: https://anchor.fm/frank-kraemer ►  schriftlicher Kontakt:SonnenkreuzPostfach 133053776 EitorfDeutschland Du willst meine Arbeit tatkräftig unterstützen:  ►  https://www.d3b-mitstreiterschaft.com/►  https://www.derdritteblickwinkel.com/unterstuetzung

König Peter vom Königreich Deutschland (KRD) war in letzter Zeit auf YouTube sehr präsent. Dazu kommen diverse Dokus im Mainstream. Ist das KRD wirklich ein echter Staat und sogar eine Alternative zur brd wo nicht einmal Steuern erhoben werden? In diesem Gespräch nimmt Frank Kraemer auch kritische Positionen auf, die über das KRD im Netz kursieren und zu denen König Peter Stellung bezieht. Hier ist der erste von zwei Teilen. Einen aktuellen Überblick zu allen Kanälen findest Du hier:►  https://linktr.ee/frankkraemer Frank Kraemer im Gespräch findest Du auf folgenden Podcast-Plattformen:►  Spotify: https://open.spotify.com/show/1QDSCBerBukKvEMLFAjHoW►  Google Podcasts: https://www.google.com/podcasts?feed=aHR0cHM6Ly9hbmNob3IuZm0vcy80YjIzYzA1OC9wb2RjYXN0L3Jzcw==►  RadioPublic: https://radiopublic.com/d3b-podcast-6LBkjL►  Pocket Casts: https://pca.st/tg41uhyf►  Anchor: https://anchor.fm/frank-kraemer ►  schriftlicher Kontakt:SonnenkreuzPostfach 133053776 EitorfDeutschland Du willst meine Arbeit tatkräftig unterstützen:  ►  https://www.d3b-mitstreiterschaft.com/►  https://www.derdritteblickwinkel.com/unterstuetzung

It is Wrestlemania week and we are chalk full of wrestling previews of the biggest week in wrestling. We catch up quickly and our wonderful listeners remind us of the Needle in the pecker spot from the XPW show this past weekend, so we talk about that for a bit. Kevin is furious & Tony is speechless, which doesn't happen often. We got Over the Top and cover all the major shows from the past week of TV, WWE, AEW, Impact, NWA, ROH and MLW. Matt isn't the biggest fan of Wrestlemania week, so we dive into that, hot dogs and more. We preview the Wrestlemania 39 card, and it seems like the gang is pretty excited, even if Omos vs Brock is on the show. A quick break to plug Patreon's and the Wizards Network Upon returning, Matt realizes that NXT Stand & Deliver is also this weekend, so we talk about the card, & Tony tries to guess if the name is one of an NXT Wrestler or a made up name by Kevin. We talk about AEW, The Dream Match between Kenny Omega and Vikingo, Stu Grayson, Sting, Adam Page, Blackpool Combat Club, Jeff Cobb and more. Bad luck has struck Impact, so we touch on the unfortunate injury to Josh Alexander and Mickie James Run down the Ring of Honor Supercard of Honor Card Then we hit on the Wizards Rewind back to Supercard of Honor 9, we run down the card, what worked for us, what we didn't like, who was in KRD, Jimmy Jacobs and Lacey, and much more. It's another great show and we hope you enjoy it. Please remember to Subscribe, Rate and Review wherever you listen to the show. --- Support this podcast: https://podcasters.spotify.com/pod/show/the-shining-wizards/support

Cannabis Business Insurance Policies that Mitigate Risk with Keith Doan #96 If you're in cannabis I bet you're a risk taker: rock climbing. snow boarding, kite surfing, does that sound like you?  I thought so. But when it comes to taking risk in your business does it make sense to take the risk and not be fully insured?  Cannabis is a wacky business and a lot of things can go wrong. That's why our guest today comes from the insurance industry. Keith Doan is the President & CEO of KRD Risk Management Consulting & Insurance Group, LLC in Frisco Texas.  KRD provides business insurance policies that are essential for cannabis companies to manage risks, comply with legal requirements, protect assets, ensure financial stability, and maintain a strong professional reputation. In this episode we go back to Las Vegas and discuss cannabis business insurance polies that mitigate risk.   The Cannabis Advocate podcast advocates for businesses in the cannabis industry and explores the unique challenges they face. Despite hurdles in legislation, regulation, and culture, there are tremendous opportunities for growers, manufacturers and retail sellers of cannabis products. Many of these issues are unique to the cannabis industry. This podcast speaks to these common concerns and shares stories of success. This is a production of Habanero Media.  https://habaneromedia.net To subscribe to the podcast go to  https://cannabisadvocatepodcast.com/listen/ If you have a question or comment, https://cannabisadvocatepodcast.com/contact

Dr Jakubowiak discusses interim findings from the ATLAS trial of KRd vs lenalidomide maintenance in patients with newly diagnosed multiple myeloma, contextualizes these data within the broader post-transplant landscape, and previews the next steps for this research.

Featuring perspectives from Dr Paul Richardson, including the following topics: Introduction (0:00) Case: A man in his early 60s with newly diagnosed Stage II standard-risk multiple myeloma — Ranju Gupta, MD (29:31) Case: A woman in her early 70s with Stage IIIA multiple myeloma who receives lenalidomide/bortezomib/dexamethasone → autologous stem cell transplant (ASCT) and discontinues maintenance lenalidomide after 3 years — Erik Rupard, MD (34:16) Case: A woman in her early 70s with relapsed myeloma after tandem ASCT who receives cyclophosphamide/bortezomib/dexamethasone, achieves minimum residual disease negativity and is now on maintenance ixazomib — Zanetta S Lamar, MD (39:01) Case: A woman in her early 70s with triple-class refractory t(11;14) multiple myeloma — Hans Lee, MD (43:47) Case: A man in his mid 60s with high-risk relapsed multiple myeloma after carfilzomib/lenalidomide/dexamethasone (KRd) induction, ASCT, maintenance KRd and 2 additional lines of therapy — Muzaffar H Qazilbash, MD (46:05) Faculty Survey (52:29) Journal Club with Dr Richardson (60:57) CME information and select publications

To celebrate our 100th year broadcasting, Terry is talking with some of the voices of WHAS past including sports reporter Jody Demling.Jody walks through his career starting at the Courier-Journal working the desk and writing articles then progressing into working on TV and radio including at NewsRadio 840 WHAS, 790 KRD and the UofL Radio Network.

Jak stworzyć zespół sprzedażowy? Jak stworzyć skuteczny zespół? Jak zarządzać telefoniczną sprzedażą? Jak zarządzać zespołem sprzedażowym? Na te i wiele innych pytań odpowie Karolina Froń. #zespołysprzedażowe #callcenter #sprzedażtelefoniczna Spis Treści: 00:00 - Wstęp 00:37 - Karolina Froń - początki drogi biznesowej 04:51 - Od czego zaczynają liderzy w firmie? 06:36 - Wyznaczanie właściwych roli i zadań 10:21 - System motywacyjny 27:52 - Silne przywództwo 29:18 - Ustalanie zasad 30:33 - Regularne zebrania 32:20 - Feedback, jak robić to dobrze 34:18 - Narzekanie w zespole 47:20 - Samodzielna praca 50:23 - Rozwój w zespole 52:53 - Podsumowanie

Muitos pacientes oncológicos têm dificuldade para entender termos médicos, como: remissão, recidiva, doença refratária, etc. Além de siglas do tratamento, como: VTD, VRD, KRD, MDT, entre outros. Por isso, neste episódio, entrevistamos a Dra. Danielle Leão, hematologista e pesquisadora clínica da BP - A Beneficência Portuguesa de São Paulo, para explicar tudo sobre os termos e tratamentos do mieloma múltiplo. Escute agora! Hosts: Bárbara Fernandes e André Torres Convidada: Dra. Danielle Leão   Site: https://www.abrale.org.br/   Instagram: www.instagram.com/abraleoficial/   Youtube: www.youtube.com/AbraleSP   Facebook: www.facebook.com/abrale   Twitter: https://twitter.com/abraleoficial Tiktok: https://www.tiktok.com/@abraleoficial

Featuring an interview with Dr Saad Zafar Usmani, including the following topics: Determining transplant eligibility for patients with newly diagnosed multiple myeloma (MM); treatment for transplant-eligible patients who decline transplant (0:00) Assessing frailty in patients with MM; underrepresentation of older patients in clinical trials (5:32) Selection of first-line therapy for transplant-ineligible patients with MM (10:55) Emerging data with daratumumab and lenalidomide/bortezomib/dexamethasone (RVd) for patients with MM; defining high-risk MM (16:56) Outcomes from the real-world community-based TOURMALINE US-MM6 trial evaluating ixazomib-based induction treatment (20:19) Efficacy and safety findings from the ENDURANCE trial comparing KRd (carfilzomib/lenalidomide/dexamethasone) to RVd (25:28) Optimal management of proteasome inhibitor-associated neuropathy; novel and emerging therapies for MM (28:52) Management of toxicities and other practical issues associated with CAR (chimeric antigen receptor) T-cell therapy for MM (34:41) CME information and select publications

The fashion industry is one of the most wasteful industries in the world, making up roughly 10% of humanity's carbon emissions, it is the second largest consumer of water worldwide, and 85% of textiles end up in landfills every year. How can we change that and what is the difference between ethics and sustainability? This week Amanda is joined by Kevin Robert Fernandez of Kevin Robert Designs, artist, designer and stylist based in Brooklyn. After realizing he enjoyed getting dressed for his job in criminal psychology more than the job itself, it was time to reevaluate and pursue what he was actually passionate about--fashion and design inspired by waste reduction and sustainability.  Amanda and Kevin talk thrift store shopping, developing your own style, and determining what stands out to each individual as far as ethical practices and what we can do on our own to support our personal missions. Everyone is capable of ethical practice, but it does require commitment. What companies actually have a good recycling program and what prevents others from participating in one at all (side eye to luxury brands).  Stay up to date with the KRD collection on Instagram Follow I have a question! on Instagram  Follow the Missing Sock Network on Instagram and support us on Patreon for access to bonus content and more! Thoughts? More questions? Email the show! Ihaveaquestionthepodcast@gmail.com

126 tysięcy złotych kary - tyle wynosi dług rekordzisty jeśli chodzi o jazdę bez biletów. W ostatnich latach liczba gapowiczów wzrosła – podaje Krajowy Rejestr Długów. Niezapłacone kary za jazdę bez biletu sięgnęły już pół miliarda złotych. Z danych KRD wynika, że najczęściej na gapę jeżdżą pasażerowie między 26. a 35. rokiem życia. Takich dłużników jest też najwięcej, bo niemal 110 tysięcy. Młodzi wygenerowali jedną trzecią długu z tytułu podróży bez biletu. ​Dlaczego jeździmy bez biletu? I co na to kierowcy?

W 127. odcinku podcastu Branżowisko zapraszamy do naszego drugiego biura. Wszystko po to, by zaprezentować Wam, jak praktycznym rozwiązaniem są ścianki działowe wyposażone w szyby ze zmienną przeziernością (o efekcie „wow”, jakie robią one na gościach, nie wspominając). Choć szyba PRIVA-LITE od Saint-Gobain Glassolutions to rozwiązanie dobrze znane na rynku, produkt ten nadal jest rozwijany, a jego zastosowanie w dobie pandemii nabrało na znaczeniu. Ponadto wspominamy nasze pierwsze webinarium po wakacyjnej przerwie, na którym poznaliśmy pierwsze premiery zapowiadane na rok 2022. Jakie produkty przygotowały firmy na przyszły sezon? Omawiamy też poziom zadłużenia firm z branży budowlanej, skupiając się na reprezentantach z naszej branży. Ile wyniosło ich zadłużenie i jakie zobowiązania ma rekordzista w świecie stolarki? Odpowiedzi znajdziecie w naszym podcaście. O tym, że bardzo wiele działo się w ubiegłym tygodniu w naszej branży niech świadczy fakt, że skrót informacji z naszego serwisu jest naprawdę bogaty! Nie zabrakło też krótkiego przeglądu ekonomicznego oraz Stoll Street, czyli naszego przeglądu wyników giełdowych spółek związanych z branżą stolarki. Miłego słuchania/oglądania!

Dr. Mitul Gandhi, medical oncologist-hematologist at Virginia Cancer Specialists of the US Oncology Network, highlights therapeutic advances in multiple myeloma featured at the 2021 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Mitul Gandhi, a medical oncologist specializing in hematologic malignancies at Virginia Cancer Specialists, which is part of the US Oncology Network. Dr. Gandhi will discuss therapeutic advances in multiple myeloma featured at the 2021 ASCO Annual Meeting. He reports no conflicts of interest relating to our discussion today, and full disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Gandhi, welcome to the ASCO Daily News podcast. Dr. Mitul Gandhi: Thank you for having me. ASCO Daily News: Let's first look at the OPTIMUM MUKnine trial. It's Abstract 8001. And it reported high overall response rates in patients with ultra high-risk multiple myeloma with Dara-CVRd induction therapy. What are your takeaways from this study, Dr. Gandhi? Dr. Mitul Gandhi: Sure. So, the OPTIMUM study was conducted by the UK group, and it's noteworthy for several reasons. The way they had constructed the trial, they designed and developed a platform primarily to enrich for a predefined subset of very high-risk individuals, whether it was through a set of genetic assessment or with central gene expression profiling. And the way the trial was conducted, while patients were waiting to ascertain the results of the gene expression profiling (GEP) they could receive two cycles of bridging therapy. Once those results were furnished or they met the cytogenetic risk criteria, patients who subsequently consented to the intervention protocol which was a dose intensified regimen, five drug regimen, incorporating daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone. So, patients would receive induction for up to six cycles, and that would include the two cycles of potential bridging therapy as GEP was being evaluated on an every 21 day basis. And then this was followed by a modified conditioning regimen consisting of high-dose melphalan at 200 milligrams per meter squared along with weekly bortezomib which was continued even following autologous stem cell rescue, really until count recovery. Subsequently, patients received an additional six cycles of daratumumab, bortezomib, revlimid, or lenalidomide followed by 12 cycles of daratumumab and rituximab until progression. This was a complex study design with an intensified induction consolidation and maintenance phase, but it did yield a impressively high OR rate, or overall response rate, at 94% with very good partial response or greater seen in 77% after assessment following autologous transplantation, including 46% complete response (CR). And of those with CR, they had identified 63% achieving MRD negativity as well. And I think the authors should be commended for one, enriching a high-risk subset of patients both on conventional cytogenetics and/or GDP, and then two, utilizing the most active agents that we currently have to elicit high responses and then to consolidate on those following transplant. I think some of the take homes from the study are the ability to demonstrate feasibility of central genomic risk stratification related to more precisely identify and select high-risk patients as this is kind of an area of unmet need of where to augment therapy appropriately. I think it's still a question whether or not this is the exact dose intensified regimen that's going to elicit the best long-term outcomes in these highest risk patients and whether or not the conventional surrogates for a long-term progression-free survival (PFS) benefits such as MRD really apply to this as there is some controversy regarding that. Nonetheless, I think this offers a kind of a reproducible platform that can be emulated to identify the highest risk patients. You can do that prospectively, and then to selectively incorporate the most active agents and potentially the next generation of novel agents, including immunomodulators, cellular therapy, bi-specific antibodies earlier in the treatment course, and really try to elicit the deepest initial response and hopefully see that translate into longer term durable control. So, this was a complex study design that was impressively executed, and again with an ability to enrich for the highest risk subsets. ASCO Daily News: Excellent. Thanks for sharing your takeaways from the OPTIMUM trial. Well let's focus on the phase II CARTITUDE-2 study. That's Abstract 8013. This study reported that deep and early responses were yielded with a single infusion of cilta-cel in patients who had received one to three prior lines of therapy for multiple myeloma. What are your thoughts on this trial? Dr. Mitul Gandhi: So, Dr. Usmani presented the CARTITUDE-2 update on behalf of his co-collaborators. And the listeners probably are aware of some of the preliminary data that was presented at ASH as well in 2020, but this is a phase I/II protocol. Currently the phase II data are being presented with a proprietary CAR T platform which has two BCMA single domain antibodies on the CAR T construct along with a co-stimulator domain. And as kind of summarized in the title, the single dose was infused. So, amongst 113 patients who were initially recruited, 97 ultimately were treated with some fallout attributed to progressive disease. Like many of the other CAR T studies, this was a uniformly high-risk and heavily pretreated population. Median age was 61. High-risk cytogenetics were in 23% of patients. And there was about 20% of patients who had harbored plasma cytomas as well. Response rates were impressively high at almost 98%, and 67% obtaining a stringent complete response (CR). Much like the other CAR T experience, response continued to deepen over time. And encouragingly, duration of response was actually not reached time of presentation. Kind of amplifying the depth of response, of the patients assessable for MRD, 93% had achieved an MRD negative state at a sensitivity of 10 to the minus fifth cells, leading to a 12-month PFS of 77% and an OS of 89%. So, these are all welcome numbers and response data, again, in a heavily pretreated population who have been exposed to what we believe all the more active agents in the disease. In parallel with kind of response, with particularly with CAR T is the toxicity data. And encouragingly, while CRS, or cytokine release syndrome, which is typified in CAR T therapy was seen in about 95% of patients, only 4% had grade 3 to 4 CRS. So, on the whole, quite manageable. Median time to onset was 7 days with duration of 4 days and resolved with appropriate medical therapy, including tocilizumab. They did report one patient who had grade 5 CRS with hemophagocytic lymphohistiocytosis (HLH) with the remainder, I was summarizing kind of the low level of grade 3, 4 experience. There was additionally neurotoxicity and 21%, with 10% having grade 3 or higher. Again, resolved with supportive care measures. So, in totality this builds on the CAR T experience with high response rates, deep response, rates including achievement of stringent CR and high rates of MRD negativity with only a single dose of CAR T cells infused, again amplifying the efficacy of this platform on a heavily pretreated population and potentially allowing for extended treatment-free intervals as well or options for retreating in people who don't achieve MRD with a manageable toxicity profile at experienced centers. Certainly there's still work that's going to be done to better delineate the extent of CRS and how to appropriately treat that along with the neurotoxicity, but along with several other abstracts presented at this meeting and meetings prior, builds on the CAR T experience, knowledge rapidly coming to the forefront in myeloma therapy. ASCO Daily News: Great. So, some good developments for previously treated patients. Well, now I'd like to focus on newly diagnosed multiple myeloma. Let's look at the CARDAMON trial, Abstract 8000, and the FORTE trial, Abstract 8002. These studies explored novel therapies that are emerging for newly diagnosed multiple myeloma. So in their presentations, these trial investigators seem to question the value of standard of care autologous stem cell transplant (ASCT). So do you think these new data call into question the advantages of the up front ASCT approach in newly diagnosed multiple myeloma? Dr. Mitul Gandhi: That's a great question. And as providers in the myeloma community know, there's still an ongoing debate whether or not to ubiquitously apply a high dose melphalan conditioning and stem cell rescue across the spectrum of all patients with myeloma who are transplant eligible or reserving it for certain patients or not. Some of this is borne out of saving unnecessarily aggressive therapy, who would otherwise achieve an excellent response of induction. Along with some concern for secondary genotoxic effects imparted by the melphalan itself and perhaps propagating more biologically aggressive subclones. And to that end, these two abstracts explored whether or not transplant-free approaches would be feasible. So, the CARDAMON study enrolled 281 patients where all patients received kyprolis, cyclophosphamide, and dexamethasone for four cycles, and of those patients achieving at least a partial response (PR), they were subsequently randomly assigned to continuous KCd or autologous stem cell transplant. And what the authors concluded, KCd induction followed by KCd maintenance was not inferior to autologous stem cell transplant with PFS at 2 years measured at 70% versus 76%, and that difference meeting the criteria that was prespecified in terms of their confidence interval for noninferiority. So, on the surface you could argue based on the results that were presented that there was equivalence. But a few caveats that are important to bring up, the first was that follow-up was short. It was only two years, and so it's very plausible that with longer follow up, the noninferiority that was seen may not be borne out with extended follow up. The other point the author's note was that MRD negativity was higher in the autologous stem cell group at 53% compared to 35.8% of the non-transplant group. And various studies have reported this to be a reasonable surrogate for long-term PFS, not always. And so again highlights the fact that with longer follow up, we may see a separation of the curves. Their subset analyses did not demonstrate any obvious areas, rather a subset of patients that would have derived preferential benefit, although the numbers were quite small. So, while an initial conclusion may be that there was a relative equivalence for a transplant-free approach, I'd argue that it's probably still a bit premature to make that conclusion and noninferiority may not be identical with longer follow up. And additionally, this probably is an induction regimen that is not as commonly employed in the U.S. But it does again help to the body of literature regarding this question of transplant for all versus not, although there may be hopefully more discriminatory power to see where it would be beneficial. The FORTE study presented by Dr. Gay and her colleagues was a bit larger at 464 patients and slightly different. Patients were randomly assigned to one of three arms, carfilzomib plus cyclophosphamide plus dexamethasone for four cycles induction followed by autologous stem cell rescue, carfilzomib, lenalidomide, dexamethasone induction for four cell cycles followed by autologous stem cell rescue, or carfilzomib, lenalidomide, dexamethasone without autologous stem cell for 12 cycles. So, those were the three arms, and then there was a second randomization to lenalidomide versus lenalidomide plus carfilzomib maintenance. Patients were prespecified in terms of their cohorts of high-risk, standard risk, or the so-called double hit which was people, patients rather, harboring two high-risk cytogenetic features. And so what the authors concluded that across the board, the arm containing carfilzomib, lenalidomide, dexamethasone with autologous stem cell rescue demonstrated superior PFS compared to all of the other, rather, the other two arms. And similarly intensification of maintenance incorporating kyprolis plus revlimid resulted in superior 3 year PFS compared to revlimid alone in 90% versus 73%. So what do we take away from this? Well, it's not a conventional induction approach in the U.S., with RVd still predominantly being used, particularly after the endurance data was presented at last year's ASCO showing equivalence of a bortezomib induction strategy versus carfilzomib strategy. It does support and lend credence to the use of high dose melphalan autologous stem cell rescue as patients who are in this arm seem to enjoy a more longer and durable progression-free survival across all subsets, including standard risk, high-risk, and the double hit strategy. So there wasn't any particular subset that could be identified that would have performed equally well with KRd alone without autologous stem cell rescue. Putting these two abstracts together, I would still argue that there remains a very important role for our high dose melphalan and autologous stem cell rescue currently an induction, rather following induction, in appropriately selected patients. And while we may not have identified patients on preselected criteria based on their cytogenetic risk, it's conceivable that we might identify response based criteria, whether it's MRD or otherwise, to perhaps see who may be able to abstain from transplantation. And there are several protocols that are actively accruing, some that have been preliminarily presented, and some that will be presented in subsequent meetings that might lend evidence to this. But for now based on the data sets that were presented at this year's meeting at ASCO, there still seems to be support for use of high dose melphalan and autologous stem cell rescue. ASCO Daily News: Right. Well staying with the issue of transplantation, for over a decade investigators have been exploring the curative ability of alloHCT in select patients with high-risk multiple myeloma. Fast forward to 2021 and the phase II double blind, placebo controlled, blood and marrow transplant clinical trials network 1302 trial. That's Abstract 7003. This study found that when performed with a reduced intensity conditioning regimen of bortezomib, fludarabine, and melphalan, alloHCT was safe in patients with high-risk multiple myeloma. What are your thoughts on this, and do you anticipate further research on the role of alloHCT in patients with multiple myeloma and high-risk features? Dr. Mitul Gandhi: So, this is an interesting abstract presented by Dr. Nishihori and her colleagues specifically looking at the role of ixazomib maintenance following a reduced intensity conditioning regimen of fludarabine, melphalan, and bortezomib in patients with high-risk myeloma. So this study was a phase II study enrolling patients under the age of 70 with high-risk myeloma defined by cytogenetics, or presence of plasma cell leukemia, or relapse within 24 months of an autologous stem cell transplant, which has been identified as a prognostic factor independent of baseline risk of poor outcomes, with the goal of administering the reduced intensity conditioning followed by HLA matched donor unmanipulated graft with methotrexate and tacrolimus GVHD prophylaxis, and starting at day 60, randomization ixazomib versus placebo maintenance. It should be noted that the goal initially was to enroll 110 patients, but ultimately only 57 patients were accrued over the course of 4 years from 2015 to 2018, 52 ultimately receiving an allogeneic HCT and 43 proceeding to maintenance. And so this in and of itself highlights the challenges of running an alginate transplant trial in myeloma mainly because sick patients may be by the point where allogeneic transplant is being entertained or inability to achieve sufficient disease control in order to pursue the transplant. But with respect to the study itself, they reported a PFS and overall survival (OS) outcome at 24 months, of 52% and 85% respectively, with transplant-related mortality at a respectable 11%. So in context of the small studies that had previously been reported in this space of allo SCT and myeloma, this was improved treatment-related mortality related to the procedure itself. With respect to the question at hand regarding the role of ixazomib maintenance, interestingly they showed no difference in PFS, with ixazomib versus placebo at 55% and 59% and OS at 95% and 87%. In terms of the toxicity, it was not trivial. Grade 3 to 4 acute GVHD at day 100 was 9.5% in the ixazomib arm, 0% in the placebo arm. And chronic GVHD was 69% versus 64%. So, where do we take all of this data in context? I think there is a signal of lower transplant-related mortality compared to historical controls, and so it probably speaks to the improved ability to identify patients and also get them through transplant with this modified conditioning. The follow up, however, was abbreviated, and so there may be increased relapse over time as well. In terms of where does this fit in the armamentarium of therapy with refractory myeloma, I think that's still to be determined. And perhaps it's going to be occupying more of a niche role given the blossoming repertoire of highly efficacious immune-based agents, whether it's modified cellular therapy with CAR T a upcoming NK cell products that are being explored, and of course by specifically antibodies that have been robustly presented at this meeting demonstrating impressive responses. So, it's very conceivable that patients who were previously would be entertained for allogeneic SCT will now be in are treated with this kind of repertoire of novel immune agents. And so it may become a more of a niche role in patients who have exhausted all conventional or investigational approaches, but it does suggest that with this modified reduced intensity conditioning, treatment-related mortality can be lowered. With respect to the question at hand, it does not appear as though maintenance ixazomib helps these patients. And so observation alone following transplant versus an alternative maintenance strategy would be indicated. ASCO Daily News: OK. Well I'd like to ask you about the Apollo trial. That's Abstract 8046. This study looked at health-related quality of life of previously treated patients with multiple myeloma on a regimen of pomalidomide and dexamethasone plus subcutaneous daratumumab. Any surprises here, Dr. Gandhi? Dr. Mitul Gandhi: So, the Apollo study is a phase III trial primarily evaluating the efficacy of pomalidomide plus dexamethasone versus pomalidomide dexamethasone plus the incorporation of subcutaneous daratumumab in patients with myeloma who had received one prior line of therapy. And primary outcomes data had already been presented with improved rates of disease control with incorporation of daratumumab. With respect to this abstract, Dr. Terpos presented quality of life and patient-reported outcomes that was collected in parallel with the intervention arm of this study, and so they utilized the EORTC 30 item questionnaire to assess quality of life and subjective data from patients. And what they found was in the patients who had been on the DPD arm, or the daratumumab arm, there was a greater reduction in pain and no real augmentation or introduction of increased adverse events related to the additional agent. Moreover, there was no decline in physical or emotional functioning with DPD, but there was worsening decline in those elements compared to baseline for patients receiving pomalidomide and dexamethasone alone. There were higher rates of improvement with respect to control of disease symptoms, physical functioning, emotional functioning on the DPD arm. So, what does this tell us? Well in general, I think we've seen a plethora of agents that have improved outcomes with our patients with myeloma who are now living for years on therapy, increasingly and often even into a second decade. And so gaging the impact of therapy on quality of life, subjective sense of well-being is critical as these patients are going to be on therapy for quite a while. And so independent of serologic and laboratory response, we certainly want the interventions to improve functional capacity. And this data would suggest that you can achieve that in parallel with achieving better and deeper responses, which intuitively makes some sense, and they are often congruous. Involving the incorporation of an additional agent didn't worsen the sense of adverse events, but in fact improved the general sense of well-being. So this adds to the body of work of daratumumab on a MM dexamethasone backbone parting benefit without toxicity and also lending credence to the notion that by improving myeloma parameters, we're going to be in parallel improving quality of life. And so with the advent of all the other agents and novel compounds that are being developed after the acute toxicity period, we'd also expect to see improvement in quality of life as well. And so I think this was an important contributor to telling us this. ASCO Daily News: Excellent. Well thank you so much, Dr. Gandhi. I really appreciate your time today. Before we wrap up, any final thoughts from you on advances in multiple myeloma? There's certainly some really impactful work being done in the field. Dr. Mitul Gandhi: Yeah. I think I would encourage all the listeners to review the abstracts presented, particularly the oral abstracts as they get into some of the granularity on detail regarding the individual CAR T and bispecific antibody products, and very nicely demonstrate the durable responses that are being achieved in heavily pre-treated patients. Obviously kind of the next sort of hurdle in the field is to democratize these agents and make sure they're readily available for all patients. And there's a lot of work being done to ensure that management of the acute toxicity can be managed more broadly. So I think I'd pay particular attention to the oral abstract sessions which really demonstrate the novel agents that are being investigated. ASCO Daily News: Dr. Gandhi, thanks again for being on the podcast today to highlight some great new therapies in multiple myeloma. Dr. Mitul Gandhi: Thank you for having me. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts.   Disclosures: Dr. Mitul Gandhi: None disclosed.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Featuring perspectives from Drs Sagar Lonial and Krina K Patel, including the following topics: Faculty Presentation — Sagar Lonial, MD Diagnosis, risk stratification and role of cytogenetics in multiple myeloma (MM) (0:00) ENDURANCE (E1A11): Results of a Phase III trial evaluating KRd (carfilzomib, lenalidomide and dexamethasone) versus Ienalidomide, bortezomib and dexamethasone (RVd) as initial therapy for patients with MM (5:16) Findings from Phase III trials evaluating daratumumab-containing front-line regimens for newly diagnosed MM (7:04) Emerging results from Phase III studies evaluating elotuzumab and ixazomib as components of induction therapy (8:40)  Factors to consider in the treatment selection for newly diagnosed versus relapsed disease (10:16) Published research with isatuximab and with selinexor for relapsed/refractory MM (12:41) Mechanism of action of selinexor; role of KRd and daratumumab for patients with high-risk MM (15:27) Case: A man in his early 60s with standard-risk MM receives RVd and daratumumab on the GRIFFIN trial (23:50) Faculty Presentation — Krina K Patel, MD, MSc Compositional and mechanistic similarities and differences among, efficacy and safety outcomes with and ongoing investigation of various B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy platforms in MM (36:26) Efficacy and safety results from studies evaluating belantamab mafodotin alone (DREAMM-2) or in combination with bortezomib/dexamethasone (DREAMM-6) for relapsed/refractory MM (59:51) Available data with novel anti-BCMA bispecific T-cell engagers for patients with MM (1:04:01) Published efficacy and safety findings with venetoclax for MM; correlation between t(11;14) status and response (1:07:07) Activity and safety of next-generation immunomodulatory agents observed in patients with heavily pretreated MM; other novel strategies in clinical development (1:11:27) Discussion of Investigator Survey with Dr Lonial and Dr Patel Induction and maintenance therapy for newly diagnosed MM (1:16:09) Management of relapsed/refractory disease (1:41:48) FDA approval of the antibody-drug conjugate belantamab mafodotin and role of BCMA-directed CAR T-cell therapies in MM (1:51:22) Future developments and novel investigational approaches in MM (2:07:14) CME information and select publications  

Nick is celebrating five years on KRD and trying to chart where Louisville could fall in the tourney after a tumultuous season. Plus, Fast Five.

FDA 批准治疗慢性免疫性血小板减少症的新药BMJ 术后血栓预防中，加压袜并不能提供额外的获益Nature子刊 白血病治疗性疫苗的研制阿凡波帕（avatrombopag）阿凡波帕（avatrombopag）血小板生成素受体激动剂。在上周三《消化科星期三 Episode 23》中已经给介绍了阿凡波帕用于治疗慢性肝病合并血小板减少患者的手术前用药，可以改善血小板计数、减少出血和输血。2019年6月，该药的适应症被扩展至慢性免疫性血小板减少。《随机对照研究：阿凡波帕治疗慢性免疫血小板减少症的3期临床研究》British Journal of Haematology，2018年11月 (1)这个安慰剂对照、多中心、随机、双盲的3阶段的研究，目的是评估阿凡波帕20mg qd治疗成人慢性、免疫性血小板减少症的疗效。研究纳入49位患者，入组时血小板计数

FDA 批准治疗慢性免疫性血小板减少症的新药BMJ 术后血栓预防中，加压袜并不能提供额外的获益Nature子刊 白血病治疗性疫苗的研制阿凡波帕（avatrombopag）阿凡波帕（avatrombopag）血小板生成素受体激动剂。在上周三《消化科星期三 Episode 23》中已经给介绍了阿凡波帕用于治疗慢性肝病合并血小板减少患者的手术前用药，可以改善血小板计数、减少出血和输血。2019年6月，该药的适应症被扩展至慢性免疫性血小板减少。《随机对照研究：阿凡波帕治疗慢性免疫血小板减少症的3期临床研究》British Journal of Haematology，2018年11月 (1)这个安慰剂对照、多中心、随机、双盲的3阶段的研究，目的是评估阿凡波帕20mg qd治疗成人慢性、免疫性血小板减少症的疗效。研究纳入49位患者，入组时血小板计数

W kolejnych tipach, wydarzeniach i zapowiedzi podcastu Prawo dla Biznesu o dziwo kolejna garść informacji na temat tego, gdzie będzie mnie można spotkać w najbliższym czasie ! Poza tym, garść informacji dotyczących ostatnio co raz częściej obserwowanych działań związanych windykacją roszczeń o ustawowe rekompensaty. Z tego odcinka dowiesz się:1) kiedy można zbyć roszczenie o ustawowe rekomepnsaty,2) kiedy dochodzenie takich roszczeń będzie stanowić nadużycie prawa,3) jak można się bronić przed tego rodzaju roszczeniami,4) jak wykreślić roszczenia z KRD.Zapraszam do słuchania ! :) Zapraszam do słuchania oraz do pobrania e-booka: Prawo dla Biznesu. IT, który jest dostępny tutaj -> http://bityl.pl/57HRZ

Встречайте 123-й выпуск подкаста, в котором у меня в гостях Иван Муратов, технический директор Первой Мониторинговой Компании в Краснодаре, активист Краснодарского ИТ сообщества и основатель бэкенд-митапа. В этом выпуске мы говорим о мониторинге подвижных объектов, то есть транспорта. Ваня рассказал про компанию и их систему мониторинга: как она устроена и работает, где и как хранится информация, немного коснулись вопроса потоков данных и их обработки. Поговорили про Internet of Things в общем и в контексте сбора данных с автотранспорта в частности. Обсудили способы хранения сообщений с датчиков в time-series базах данных и не только. Отдельно Ваня подробно рассказал про использование TimescaleDB и PostgreSQL, как они работают, как устроено хранение, партиции и запросы. Так же мы поговорили про конференции и сообщество. Ваня рассказал как зараждалось Краснодарское айти-сообщество, про конференции «Krasnodar Dev Days» (https://krd.dev/events), их принципы, подходы и организацию. Ссылки на ресурсы по темам выпуска: * Мероприятия IT-сообщества «Krasnodar Dev Days» (https://krd.dev/events) * Ютуб канал с записями со всех конференций Krasnodar Dev Days (https://www.youtube.com/c/krddevdays) * Телеграм группа Krd.dev (https://t.me/krddevdays) Понравился выпуск? — Поддержи подкаст на patreon.com/KSDaemon (https://www.patreon.com/KSDaemon), звёздочками в iTunes (https://podcasts.apple.com/ru/podcast/software-development-podcast/id890468606?l=en), а так же ретвитом или постом! Заходи в телеграм-чат SDCast (https://t.me/SDCast), где можно обсудить выпуски, предложить гостей и высказать свои замечания и пожелания!

Dr. Mitul Gandhi, a medical oncologist specializing in hematologic malignancies at Virginia Cancer Specialists, which is part of the US Oncology Network, highlights key abstracts from the #ASCO20 Virtual Scientific Program that aim to improve outcomes for patients with multiple myeloma. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. I'm delighted to welcome Dr. Mitul Gandhi, a medical oncologist with Virginia Cancer Specialists, which is part of the US Oncology Network. Dr. Gandhi's clinical and research focus is in malignant hematology.   Today he will highlight key abstracts featured at the ASCO20 Virtual Scientific Program and discuss the potential of new agents and treatment approaches to improve outcomes for patients with multiple myeloma. Dr. Gandhi reports no financial conflicts of interest relating to the issues discussed in this podcast. Full disclosure is relating to all daily news podcasts can be found on our episode pages.   Dr. Gandhi, welcome to the ASCO Daily News Podcast.   Dr. Mitul Gandhi: Thank you for having me. I really appreciate the opportunity to review the abstracts from this year's meeting.   ASCO Daily News: Can you tell us about the abstracts that will likely support new standards of care?   Dr. Mitul Gandhi: So within the world of multiple myeloma, there were several exciting studies that were conducted with investigational agents that are new, and then repurposing existing agents in different lines of therapy. When reviewing this, while it may not change how we practice tomorrow, it certainly informs what may be in the very near future.   I think a representative abstract is 8500, presented by Dr. Richardson and his colleagues, and involved a novel compound CC-92480 in relapsed refractory myeloma. And this is an interesting compound, which is a Cereblon ligase modulator and a next iteration of agent based on the Revlimid and, rather, lenalidomide and pomalidomide mechanism acting on Cereblon and degrading Ikaros and Aiolos.   And this was a phase I study with a phase II expansion based on the maximally tolerated dose. And what they found were that this agent studied in heavily pretreated myeloma patients, all refractory lenalidomide, pomalidomide in the majority refractory to anti-CD38 antibodies. This drug was still able to achieve a response across several dosing cohorts.   They had a complex study design involving twice daily along with once daily dosing, and a 1.0 milligram-per-day dose was identified as a MTD. And at that dose, they found 48% of patients achieved a response, with correlative studies demonstrating degradation in Ikaros and Aiolos consistent with the mechanism of action.    And so what it tells us is that this mechanism still remains a potent avenue for exploitation in spite of progression on first- and second-rate generation compounds like lenalidomide and pomalidomide. So this informs possible changes in the future, where we would continue to use a compound like CC-92480 in spite of progression on the existing agents.   And we can see itself working in earlier lines of study and complexing with other compounds to the increased response rate. So this is something that we think will be relevant in the future if not relevant tomorrow in terms of standard of care.   ASCO Daily News: There have been substantial improvements in survival for patients with multiple myeloma in recent years, thanks to the introduction and widespread use of multiple novel agents and regimens. Are there new treatment approaches or agents in development that people should be aware of?   Dr. Mitul Gandhi: Absolutely. I think this can be viewed in a few ways. As all the listeners are well aware of and have experience with, the monoclonal antibodies on top of the existing backbone of treatment that has led to significant improvement and outcomes with relapsed refractory patients, both with daratumumab and elotuzumab.   Daratumumab, of course, being in an anti-CD38 antibody and elotuzumab targeting SLAMF7. There are next-generation antibodies on the anti-CD38 backbone, such as isatuximab. And that was studied in abstract 8508 in high-risk multiple myeloma by Dr. Weisel and colleagues from Germany.   So this particular study kind of captures what the goal is, which are moving these monoclonal antibodies higher up in the lines of therapy. So this particular trial looked at higher risk multiple myeloma, defined by chromosomal aberrations, such as deletion 17p, translocation (4;14) or (14;16), or excess copies of 1q21.   These patients received isatuximab on top of the KRd backbone, with an option for pursuing stem cell transplantation. There were 50 patients in the initially presented data -- 46 in the transplant eligible; 4 in the transplant ineligible. And one of the striking things that was identified was a 46% complete response rate in a otherwise high-risk cohort.   So this is emblematic of what the field is moving towards, which is incorporating these novel antibodies on top of an established backbone and seeing better response rate that were initially met. And as an increasing amount of data identifies achieving lower and lower myeloma burden and hopefully MRD negativity, minimal residual disease negativity, earlier on, pretending long-term, better outcomes, incorporation of these novel antibodies is one - exciting, and two - it will hopefully help inform the next generation of therapy.   Notably, these results are still preliminary phase II studies. And longer term follow up will be needed to identify if they are better than the existing outcome. Another study in that same vein is abstract 8507, presented by Dr. Zafar and his colleagues from SWOG, incorporating elotuzumab with the RVd backbone for, again, newly diagnosed, high-risk multiple myeloma.   They define high risk in a similar vein as a German group with translocation (14;16), (14;20), 17 p or gain of 1q21. And they took 103 patients, randomized them to RVd or RVd plus elotuzumab. They found at 53 months median follow up, a relative similarity in the progression-free survival. 31 months for RVd and 34 months for elo RVd with a P value of 0.449.   And there was no overall survival observed, albeit that truncated follow up. Notably, there were higher rates of response with the incorporation of elotuzumab. And so what this study validated is it's certainly using the proteasome inhibitor backbone. But maybe switching the antibody to increase response rates has, at least at this first analysis, there was no improvement in PFS.   Nonetheless, I think it's an important study, as the goal seems to be incorporating novel compounds on top of an existing backbone to improve depth of response. So these are two representative abstracts, which shows where the field is moving. And the patients that are relapsed and refractory, a slew of other studies targeting anti-BCMA are particularly exciting and relevant.   The DREAMM-6 study, abstract 8502, presented by Dr. Nooka,  used belantamab, which is an antibody drug conjugate targeting the BCMA B-cell maturation antigen conjugated to a cytotoxic payload. And in heavily pre-treated penta-refractory patients, they achieved an impressive response rate, with a clinical benefit rate of almost 80%, which is exciting, as these are patients with limited treatment options.   This is a novel mechanism of action with evidence of excellent responses, many that seem to be durable. It did have a unique toxicity profile, which is increasingly being recognized with cutaneous toxicity. So incorporation of opthalmology and identification of mitigation strategies are going to be important as more familiarity is gained.   But there are a number of further studies that are being pursued with belantamab. In context of this, there were three cellular therapy protocols also presented -- abstract 8503 by Dr. Munshi and colleagues, and abstract 8504 by Dr. Mailankody and colleagues, and abstract 8505 by Dr. Berdeja and colleagues. All three were abstracts around cellular therapy using a CAR T construct targeting BCMA with three different compounds.   And all three looked at similar patient populations with heavily pretreated patients. Abstract 8503 by Dr. Munshi looked at 140 patients penta-refractory and triple-class refractory that were treated with this compound in escalating doses. They found at the highest dose cohort at 450 times 10 to the 6 cells, an overall response rate of almost 82%, many of them durable with durability at median of 11 months.   This was associated with cytokine release storm along with some neurotoxicity, both at night, rather, at 96% and 20%, respectively-- but well managed. Similar findings were found on the other cellular products. Orvacabtagene presented by Dr. Mailankody on abstract 8504 and a Juno product in abstract 8505 by Dr. Berdeja. There was evidence of cytokine release and neurotoxicity in both. But again, with significant response rates in heavily treated patients, many of them durable. So altogether, it shows that an  extension beyond what we discussed initially, where there is next generation of compounds on existing mechanism of actions, these series of abstracts are looking at incorporation of monoclonal antibodies, improving on outcomes in first-line therapy, along with targeting BCMA through either an antibody drug conjugate or through cellular therapy, eliciting responses in very heavily pre-treated patients. Many of them are durable. But with a unique set of toxicities ranging from cutaneous to cytokine release storm.   ASCO Daily News: Dr. Gandhi, are there any other clinical trials that really stood out for you this year?   Dr. Mitul Gandhi: So a few other abstracts I think that are worth noting, with respect to the clinical trials question, I think with the data that's been presented in the abstracts we've talked about, they inform the next generation of studies as we build upon the outcomes that were presented for more mature data, longer term data, and novel combinations.   A few other studies that I think were informative -- abstract 8509, presented by Dr. Kumar and colleagues, involving venetoclax plus bortezomib and dexamethasone in relapsed refractory myeloma. This was interesting because we know that venetoclax seems to have preferential sensitivity and rearranged (11;14) patients for BCL-2 high.   And what the study found in a randomized fashion of 291 patients-- 194 to the venetoclax arm and 97 of the placebo-- in the patients that had a rearranged (11;14) translocation were felt to have BCL-2 high, median duration of PFS was not reached compared to 9.9 months in the placebo arm.   So this is an impressive targeted therapy in a subset of patients. It seems to enjoy very long-term responses in spite of being heavily pretreated with venetoclax, which is a drug that's increasingly gaining experience across a wide swath of hematologic malignancies. And so it speaks to the heterogeneity of this disease and perhaps targeting on a more genomically stratified approach with these targeted compounds.   There are a few other studies I think might be relevant for practical matters on a day-to-day basis in the clinic. One of them was 8518, presented by Dr. Ailawadhi and colleagues, regarding the use of RVd in newly diagnosed myeloma with renal impairment. As we know, many of our patients can present with myeloma-associated kidney dysfunction, whether through light-chain deposition disease or a cast nephropathy with high light-chain levels.   And there sometimes is a bit of a trepidation in administering Revlimid in this setting out of concern for toxicity in the setting of depressed GFR. They performed a retrospective analysis and found that even in patients with baseline depressed GFR ranging from less than 30 or between 30 and 60, the incorporation of lenalidomide helped achieve almost equivalent outcomes in patients compared to patients who had a preserved GFR greater than 60.   So in their transplant-ineligible patients, for example, they found a median PFS of 36 months compared to 30 months in people with and without creatinine clearance less than 60. In their transplant-eligible patients, interestingly, they found a PFS of 48 months versus 43 months in the same cohort. So this speaks to the ability to safely administer this drug in achieving nearly equivalent outcomes compared to the people who have baseline intact kidney function.   So with appropriate monitoring, modification of dosing, and attention to myelosuppression, it seems as though we should be using lenalidomide-based induction therapy, which we would otherwise would if the patient's GFR was preserved and still able to achieve long-term durable responses.   A couple of other smaller studies that I think are worth mentioning include abstract 8515, presented by Dr. Cornell and colleagues, regarding bortezomib induction in light-chain amyloidosis prior to autologous stem cell transplant. There has been some question regarding what the best induction strategy is in patients who presented with light-chain amyloid.   And so this was a retrospective analysis of the CIBMTR database. We're looking at patients who had received a bortezomib-based induction versus no induction prior to proceeding with a stem cell transplant using high-dose melphalan. And it was fairly clear in their followup that a bortezomib-based induction was associated with decreased risk of relapse within two years -- 13% in the bortezomib arm versus 22% in the patients that presented directly to transplant -- and translated into overall longer PFS as well.   So this validates the use of bortezomib in patients prior to stem cell transplantation in a niche population with amyloid. Similarly, abstract 8516, presented by Dr. Zhang and colleagues, questioned whether the incorporation of an alkyqlating agent on top of this proteasome inhibitor backbone would help in these patients with light-chain amyloid.   There has been an increased use of cyclophosphamide, bortezomib, dexamethasone induction based on smaller phase II studies. So this group looked at retrospectively a bortezomib plus an alkylating backbone versus one with bortezomib alone. And found that the overall hematologic response rate was fairly similar -- 73% in the patients that received bortezomib plus an alkylator versus 85% that did not, which was not statistically significant.   So it seems as though while there is a temptation to use the alkylator, it may not be necessary. And bortezomib alone may be sufficient. But of course, it would be on a case-by-case basis. But it adds to the body of literature regarding how to treat these patients with amyloid. So I thought those were helpful analyses in a smaller population but which may be relevant tomorrow in clinic.   ASCO Daily News: Well, thank you, Dr. Gandhi, for sharing your valuable insights on these promising developments in this field.   Dr. Mitul Gandhi: Thank you for the opportunity. I appreciate it.   ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us on Apple Podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was delighted to speak to Shaji Kumar, Mayo Clinic, Rochester, US. We asked: Should we use carfilzomib, lenalidomide, and dexamethasone (KRd) or bortezomib, lenalidomide, and dexamethasone (VRd) for patients with newly diagnosed multiple myeloma (NDMM)? In this podcast he describes the results of the ENDURANCE (E1A11) phase III trial.Shaji Kumar discusses the results of the primary endpoints: progression-free survival, and duration of therapy, as well as the secondary endpoints: MRD-negativity, overall survival, and toxicity. He also discusses quality of life metrics, including renal and neurotoxicity-related symptoms. As this study excluded high-risk patients, Shaji Kumar briefly describes the results of another trial (S1221) that enrolled a high-risk patient population to fully answer the question. Hosted on Acast. See acast.com/privacy for more information.

John Fanta and Kim Adams are joined by Nick Coffey of 790 KRD and TheCardinalConnect.com to discuss the NCAA notice of allegations against Louisville and how the administration plans to fight them. Plus Wake Forest turns to a hoop lifer to turn around its program.

Today on The Redzone, Nick is joined by his favorite fill in producer to discuss work Christmas parties, Lamar Jackson, and UL Basketball. Only on 790 KRD!

Today on the RedZone, Nick is joined by his favorite fill in producer to talk bowl games, coaches pranks, and we talk with Vince Tyra of UL and the voice of the cards, Paul Rogers. Only on 790 KRD!

Mike Rutherford of SB Nation and 790-KRD in Louisville joins Jackson to preview the 2019-20 college basketball season. Read Mike's Work: https://www.sbnation.com/authors/mike-rutherford Follow Mike: https://twitter.com/CardChronicle Visit the Podcast Website: https://jacksonneillpodcasts.com Follow Jackson on Twitter: https://twitter.com/jacksonneill20 Follow Jackson on Instagram: https://www.instagram.com/jacksonneill20/ Become a Member of Jackson's Podcasts and Gain Access to Exclusive Content: https://www.patreon.com/jacksonneill20 The Jackson Neill Sports Podcast is published on Monday, Wednesday, and Friday. Check out the Jackson Neill Podcast website for the Anything Goes w/ Jackson Neill podcast and his music podcast. Anything Goes is published on Tuesday's and Thursday's while his music podcast is released on Sunday's. Music: "cdk - Sunday" by Analog By Nature (http://dig.ccmixter.org/files/cdk/53755) 11-8-19

Nick is joined by his favorite fill in producer, Clint, to talk fan turnout at football games, Chris Mack media day comments, and NBA / NFL updates. Tune in every morning on 790 KRD from 7-10am!

Nick takes your calls after the tough loss to Clemson on 790 KRD!

On this edition of Redzone Reaction Nick celebrates a close victory over Boston College with your calls and texts and a break down of the game. Only on 790 KRD!

Nick Coffey from 790 KRD talks about an incident involving his daughter at a restaurant with Leland and Tony Vanetti on The Twisted View. Also, this week's episode of Real or Fake.

Meet The Professors: Key Questions and Emerging Research in the Management of Lymphoma, Chronic Lymphocytic Leukemia and Multiple Myeloma — Part 2: A special video supplement to a CME symposium held at the 2019 ASCO Annual Meeting featuring Dr Raje’s comments on the application of emerging research to patient care: Updated risk-stratification model incorporating the revised IMWG diagnostic criteria for smoldering multiple myeloma (MM)  (0:00) Role of imaging in the monitoring and management of MM (5:07) Perspective on the progression-free survival improvement with lenalidomide compared to observation alone for patients with asymptomatic high-risk smoldering MM treated on the Phase III ECOG-E3A06 trial (6:49) Results of the Phase III CASSIOPEIA study evaluating the addition of daratumumab to bortezomib/thalidomide/dexamethasone for newly diagnosed MM in patients eligible for autologous stem cell transplant (ASCT) (9:19) Emerging data from the Phase III MAIA trial evaluating lenalidomide/dexamethasone (Rd) with or without daratumumab for patients with newly diagnosed MM who are not candidates for ASCT (11:32) Role of MRD assessment in clinical decision-making (15:09) Results of the Phase III FORTE trial: Efficacy of carfilzomib/Rd (KRd) with or without ASCT for newly diagnosed MM according to risk status (19:31) Status of the ongoing Phase III ECOG-E1A11 (ENDURANCE) trial: Bortezomib/Rd versus KRd followed by limited or indefinite maintenance lenalidomide for symptomatic newly diagnosed MM (22:53) Clinical experience with and mitigation of differing side effects of bortezomib and carfilzomib (24:29) Appropriate use of oral ixazomib as maintenance therapy after ASCT (26:24) Dose, duration and tolerability of maintenance lenalidomide (29:49) Therapeutic options for patients with MM experiencing disease relapse on maintenance lenalidomide  (33:12) COLUMBA trial: Efficacy and safety of subcutaneous versus intravenous administration of daratumumab for patients with R/R MM (35:36) Similarities and differences between the anti-CD38 antibodies daratumumab and isatuximab (37:47) Melflufen: Novel mechanism of action and structural comparison to standard melphalan (39:47) Overexpression of Bcl-2 in patients with t(11;14) MM and rationale for the use of venetoclax  (41:42) Activity and tolerability of anti-B-cell maturation antigen (BCMA) CAR T-cell therapy in patients with MM (45:40) Use of a bispecific T-cell engager to target BCMA and CD3 in patients with MM; early efficacy and safety data with AMG 420 (49:55) Incidence and management of cytokine release syndrome and neurotoxicity associated with anti-BCMA CAR T-cell therapy for MM (52:39) Future directions for CAR T-cell therapy in MM (55:09) CME information and select publications  

Louisville Baseball Head Coach Dan McDonnell joins Ramsey & Rutherford on 790 KRD to recap the Cards' deep run in the College World Series, the controversy around pitcher Luke Smith and what's next for the team heading into the 2020 season.

Where is the line when it come to tough coaching? Arnie Spanier and Aaron Torres react to the social media outcry surrounding Michigan State HC Tom Izzo getting in the face of one of his players during the opening weekend of the NCAA Tournament. Was Izzo in the wrong or is a case of people overreacting to some tough love? The guys also discuss LeBron and the Los Angeles Lakers missing the playoffs and how Lonzo Ball has grown up over the course of this lost season.  Fox Sports Radio's Bernie Fratto joins the show to tell you where the money is moving forward in March Madness and Nick Coffey from 790 KRD in Louisville joins the show to talk more college hoops! Learn more about your ad-choices at https://news.iheart.com/podcast-advertisers

Howie introduces the new morning host for KRD and says goodbye was a positive message.

If our interview with Mike Rutherford helped us understand one thing very clearly, it's not to ever underestimate Louisville. That word of advice also applies to Rutherford as he proved he's still got 'it' as you'll find out in the podcast. We're not giving that part away so you'll have to listen. You'll find out about a resurging Cardinals men's basketball team under the guidance of Chris Mack. Then, the impact Scott Satterfield will have on the football program. Break out your dictionaries as Will Ojanen, Xayveon and Jim Quist talk with special guest Mike Rutherford (SB Nation, Card Chronicle, 790 KRD) on episode #153 of ACC Nation Podcast. The nice thing about today's media is that you're not limited in your selection. There's more sources for sports fans than ever. If you're a fan of Louisville you can certainly keep in touch with what's happening via Card Chronicle. And, if you don't live in the metro Louisville area you can still listen to Mike Rutherford (Ramsey and Rutherford) weekday afternoons beginning at 3:00pm ET via the streaming link at 790 KRD. Your familiarity with Rutherford should extend into social media as well. We thought you might be interested in taking a closer look at what's going on at Louisville as we hit mid February. The thought is that the Cardinals will be headed to the NCAA's this year. However, there's still plenty of question marks hovering around the program. And, football is easing back into the conversation as well. With a new coach at the helm you'll get Rutherford's take on the program. Mike Rutherford - Still Got 'It' But First This....Will with a wrap of ACC men's basketballSome thoughts on Duke's performance vs Virginia A lot of men ask - "What Do Women Want?" Besides love, affection, success and prosperity, it's very simple: Women Want Gabriel. Fine Jewelry Everyday. Shop now. Some of the '100 Things Louisville' 9:45Are the Cardinals 'overachievers'? 10:15What is the biggest challenge for this team? 11:59What are the expectations for Louisville basketball? 13:41Fill in the blank 15:07Beating a 'dead horse' moment - Pitino 17:32Is there any sense of 'gloom and doom' hanging over the school? 19:26Is Chris Mack the leading candidate for ACC Coach of the Year? 22:44What are fans saying about Louisville basketball? 23:46The 'exciting recruits' are? 25:09When did people realize Louisville was 'for real'? 26:57What's behind Jordan Nwora improving his game? 28:06 Mike Rutherford - Still Got 'It' Date Smarter, Not Harder. Join eharmony Today! The moment of truthLouisville football moves on to the next phase 31:56The immediate contributors on offense and defense 34:39The difference between what was and what is 36:32How did '100 Things Louisville' get started and where can you buy a copy? 38:18Sports, sports and more sports 40:25Social media connections 42:47 Mike Rutherford - Still Got 'It'

Rob Dauster of NBC Sports' College Basketball Talk joins Nick Coffey in the Red Zone on 790 KRD.

Today Nick talks Christmas parties, UL basketball, and is joined by a myriad of guests. All on The Red Zone on 790 KRD.

Episode #15 with Nick Coffey: The host of The Red Zone on 790 KRD and creator of TheCardinalConnect.com joins Billy Rutledge to talk: (1:10-12:10) -The Governor's Cup: Kentucky vs Louisville -Bobby Petrino out. Jeff Brohm in? -Kentucky Football's bright future? (15:10-25:15) -Lamar Jackson in the NFL -Thanksgiving Traditions -Tiger vs Phil (25:15-38:00) -New Bill discriminating smokers in KY -Cig stories -And rapid fire Also the Sounds of the Week which include Tiger Woods, Klay Thompson and Les Miles.

Today on The Red Zone Nick talks UL Basketball, Kiss Cam horror stories, and special guests Zach Barnett and Aaron Torres on 790 KRD!

Nick reacts to the Cards' loss vs Georgia Tech and takes your phone calls. You can also hear Bobby Petrino's press conference LIVE on 790 KRD.

Call your family and check in! Pray for our black girls who were robbed of life. Pray for the world. We the people! We are love! --- Support this podcast: https://anchor.fm/KRD/support

@Drake goes #1——— What is #GMWA ? --- Support this podcast: https://anchor.fm/KRD/support

This is dedicated to those people who work with those people who act like the manager or owner but is only an employee just like you.. --- Support this podcast: https://anchor.fm/KRD/support

What are you and your friends talking about on the phone? I’ll tell you about mines! #HappyPride #LGBQT what’s that? Happy birthday @Lala #Justiceforjunior --- Support this podcast: https://anchor.fm/KRD/support

WE ARE PEOPLE NOT A COUNTRY FORGET COLORS FORGET BORDERS WHAT WHAT ABOUT BEING A PERSON? #Savethechildren #LOVEISEVERYTHING --- Support this podcast: https://anchor.fm/KRD/support

#Jayz #Beyonce #Everythingislove --- Support this podcast: https://anchor.fm/KRD/support

Talked @Donaldtrump and @Kimkardashianwest if they can do it so can you!❤️ --- Support this podcast: https://anchor.fm/KRD/support

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John and Mike react to the breaking news that Tom Jurich will not be retained as AD. They take your phone calls and more on 790 KRD.

Howie has thoughts on the new lease for Louisville at the Yum! Center and how it went down. Plus, Tom Farmer talks soccer as KRD paints the station purple for Lou City FC.

Ep. 8: JD Coffey Interview- "The RedZone" 790 KRD by Alpha Sports

After a two week hiatus, The Matt Jones Podcast is back with a winning trifecta of guests.  Matt brings on a new UofL guy, our friend from Inside the Red Zone on 790-KRD, Nick Coffey.  Then he's joined by Alex Kennedy of Basketball Insiders to discuss the NBA Playoffs.  The episode is capped off by an appearance from Jonathan Martin of The New York Times, the podcast's resident political correspondent.  Highlights: --  Do Louisville fans still want Pitino back? --  Ranking the UK players in the NBA. --  Fallout from the Kentucky Primary. --  Can The Donald be our nation's next president? You can have every podcast delivered straight to your phone by searching for “The Matt Jones Podcast” on iTunes and clicking “subscribe.” It doesn't get much easier than that. If you aren't an iTunes person, you can also stream every podcast on Podbay or check it out on the Stitcher app. Learn more about your ad choices. Visit megaphone.fm/adchoices

ROH TV 4/25/15; Lucha Underground ep 24(The Addiction vs reDRagon)(Revealing of KRD)(Trios Tournament Final)My review of one of my favorite matches of all time and its significance in the business.