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Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. 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. 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. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

In this week's episode, we'll learn about using AI to assess transplant risk in myelofibrosis. In a step toward personalized medicine, researchers report on a machine learning model that identifies 25% of patients with poor outcomes. After that: preventing priapism in men with sickle cell anemia. A recent phase 2 feasibility study shows high rates of recruitment, retention, and adherence to oral therapies, coupled with a significant reduction in the risk of this difficult complication. Finally, new research indicates that hallmarks of terminal T-cell exhaustion are absent in multiple myeloma, from diagnosis through maintenance therapy. We explore these provocative and counterintuitive findings arising from profiling of blood and marrow samples.Featured Articles:Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosisA controlled trial for preventing priapism in sickle cell anemia: hydroxyurea plus placebo vs hydroxyurea plus tadalafilHallmarks of T-cell exhaustion and antigen experience are absent in multiple myeloma from diagnosis to maintenance therapy

In this podcast episode, we discuss clinical trial updates in chronic lymphocytic leukemia from the 2025 European Hematology Association annual congress in Milan, Italy and the 18th International Conference on Malignant Lymphoma in Lugano, Switzerland. The discussion involves an analysis of the data from abstracts investigating combination and novel therapies for the treatment of CLL.Our Host:Dr. Constantine Tam is Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University in Melbourne, Australia. Prior to joining Alfred, Dr. Tam completed a Leukemia Fellowship at MD Anderson Cancer Centre in Houston, Texas and served as Disease Group Lead for Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre & Royal Melbourne Hospital for over 10 years. He is the global lead for the BTK inhibitor zanubrutinib, overseeing its development from the first human dosed to international licensing studies. He also played key roles in the first global study of ibrutinib and venetoclax in CLL and the pivotal study of Tisagenlecleucel in diffuse large B-cell lymphoma.Our guests:Dr. John Gribben is Consultant Hematologist and Medical Oncologist at the Barts Cancer Institute, Barts NHS Trust and Professor in Medical Oncology at The London School of Medicine, Queen Mary University of London, in London, UK. Dr. Gribben trained in Haematology at University College London and in Medical Oncology at the Dana-Farber Cancer Institute, Harvard Medical School, where he remained on the faculty for 17 years before returning to the UK. Dr. Gribben serves on many international committees, including as Chair of the international workshop for NHL, co-Chair of the international workshop for CART, and founding member of the CLL Research Consortium. He also serves as an executive board member of the European Hematology Association, where he previously served as President from 2019-2021.Dr. Stephan Stilgenbauer is professor of medicine and Medical Director of the Comprehensive Cancer Center Ulm (CCCU), Head Early Clinical Trials Unit (ECTU), and Head Division of CLL Dept. of Internal Medicine III at Ulm University, Germany. He received his medical training at Heidelberg Medical School, Germany, and was trained in internal medicine and hematology-oncology at the Universities of Heidelberg and Ulm. He spent a postdoctoral fellowship at the German Cancer Research Center (DKFZ) in Heidelberg. His research focus is on the molecular pathogenesis and evolution as well as development of novel treatment strategies in hematological malignancies.If you enjoyed our podcast episode, please review and subscribe. For other medical education content, visit our website at: https://www.impactmedicom.com (https://www.impactmedicom.com/)

CooperationThe big go-cart race is coming up. But without teamwork, The Club discovers just how hard it is to be on the winning team. To support this ministry financially, visit: https://www.oneplace.com/donate/198/29

Programa de Radio No.349, Podcast No.498Transmitido el 25 de junio de 2025 por Radio y TV. Querétaro 100.3 FMEn este episodio Pablo Naop, nos hace una comparativa muy interesante de las diversas mecánicas que tiene este grandioso compilado de videojuegos, con algunos juegos de mesa, también escucharemos su banda sonora que esta inspirada en la mítica consola PC Engine; sin duda un interesante episodio que nos trasladará a la esencia de los videojuegos de 8BIt pero con toda la tecnología de la actualidad para extender desde su dificultad hasta su historia. 

In the second installment of this two-part series, Dr. Jeff Ratliff and Dr. Brin E. Freund discuss clinical guidance for managing patients who may experience neurotoxicity from CAR T-cell, with a specific focus on seizure risk.  Show reference:  https://www.neurology.org/doi/10.1212/WNL.0000000000213535 

Amy was surprised to find a miscellaneous item in her cart after she walked away from it to start her car in the parking lot.

Les footballeurs parlent aux footballeurs ! « Rothen s'enflamme », le rendez-vous des passionnés du ballon rond revient pour une deuxième saison !

Les footballeurs parlent aux footballeurs ! « Rothen s'enflamme », le rendez-vous des passionnés du ballon rond revient pour une deuxième saison !

Eric Ruderman, MD, leads a Northwestern Medicine panel discussion with Irene Blanco, MD, Anisha Dua, MD, and Carrie Richardson, MD. Together, they dive into the latest advances in clinical trials and treatment strategies for scleroderma, vasculitis and lupus.The panel discusses the goals and complexities of contemporary clinical trials, recent breakthroughs in therapies and the innovative potential of CAR-T therapy for managing autoimmune diseases. They emphasize the significance of personalized medicine and the collaboration needed among clinicians, industry collaborators and patient advocacy groups to drive research forward.

I'm CT…  When I'm not busy being Arroe the podcaster, I live in the real world.  Everybody has to have a job.  Mine is C.S.  Customer Service.  Solutions, relationships while keeping my team motivated to keep a constant connection with each guest who's chosen to stop their day to visit our location.  Episode 181 The team Isn't jelling, big super clean and locking cart syndrome This is C.T.C.S.Become a supporter of this podcast: https://www.spreaker.com/podcast/arroe-collins-like-it-s-live--4113802/support.

Buenas noches investigadores!!! Que gusto da grabar episodios sin imprevistos, sin jaleos, sin retrasos más allá de los habituales. Y esta semana con cositas muy interesantes, tanto en los comentarios como en las noticias. Con 6 investigadores para el juego de rol, con un AMA con Nick Kory y más mandaga. Pero es que además tenemos una de esas secciones que podríais pensar que van a pasar de puntillas, pero que creo que van a dejar poso y le van a venir de lujo a mucha gente (entre ellos a mi). Hoy ponemos sobre la mesa las cartas con el rasgo Doble, llevan entre nosotros poco tiempo y tal vez estén un poco desubicadas, pero para eso estamos nosotros. Esperamos que os guste.Abrasacos. Arkham Advertiser: 01:13:35 Universidad Miskatonic: 02:00:03

L'Ospedale San Bortolo di Vicenza festeggia 100 pazienti trasfusi con il metodo Car-T per la cura di leucemie e linfomi. "Un orgoglio veneto e nazionale", è stato il commento di Manuela Lanzarin. "Partiti nel 2020, la Regione ci ha creduto subito e continuerà a crederci”, ha dichiarato l'asessore regionale alla Sanità.

This week, the gals invite Irish icon Katie Charlwood of Who Did What Now Podcast to chat about the dangers of piracy (and also toddlers), some sticky handrails, a horrible hookup, brownie temptation, a coffin catastrophe, and a long-winded obit from one very lucky man. Tune in for June's Gossip at the Corpse Cart! For a full list of show sponsors, visit https://wineandcrimepodcast.com/sponsors. To advertise on Wine & Crime, please email ad-sales@libsyn.com or go to advertising.libsyn.com/winecrime.

In this week's episode, we'll learn more about social determinants of health that impact access to allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia, or AML; use of megakaryocyte growth factor receptor-based stem cell depletion as part of pretransplant conditioning in ex vivo autologous gene therapy; and identification of an eight-protein risk signature as well as a novel single protein biomarker, soluble oncostatin M receptor, for risk stratification in AML.Featured Articles:Social Determinants of Health and Access to Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid LeukemiacMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pretransplant ConditioningBlood-Based Proteomic Profiling Identifies OSMR as a Novel Biomarker of AML Outcomes

I'm CT…  When I'm not busy being Arroe the podcaster, I live in the real world.  Everybody has to have a job.  Mine is C.S.  Customer Service.  Solutions, relationships while keeping my team motivated to keep a constant connection with each guest who's chosen to stop their day to visit our location.  Episode 181 The team Isn't jelling, big super clean and locking cart syndrome This is C.T.C.S.Become a supporter of this podcast: https://www.spreaker.com/podcast/arroe-collins-unplugged-totally-uncut--994165/support.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Matthew Lunning, DO, FACP Despite FDA approvals and growing clinical integration, CAR T-cell therapies remain clouded by misconceptions, some of which could impact clinical decision-making and delay appropriate referrals. To help set the record straight on CAR T-cell therapy, Dr. Charles Turck speaks with Dr. Matthew Lunning about the realities of patient selection, safety, and access. Dr. Lunning is an Associate Professor in the Division of Hematology/Oncology at the University of Nebraska Medical Center.

This week we revisit an episode that made it out of the groupchat. Besties of the pod Casey Wilson and Danielle Schneider of Bitch Sesh join the Aunties to catch up. First, SuChin regales them with tales of laser treatments in South Korea, which means they’ll be adding to cart some plane tickets soon. Then, Danielle shares an inspiring book and Casey is swayed by a 24-year-old beauty influencer. We’re all about the yin and yang here. We want to hear from you! Drop us a message on Speakpipe. Subscribe to the Add to Cart newsletter for juicy extras. Please note, Add To Cart contains mature themes and may not be appropriate for all listeners. To see all products mentioned in this episode, head to @addtocartpod on Instagram. To purchase any of the products, see below. Shoutout to Casey’s derm, Dr. Jennifer Segal of Metropolitan Dermatology Institute The Island of Sea Women by Lisa See is a beautiful story about female divers in Korea The Last of the Sea Women documentary dives into this as well The Alastin Skincare’s TransFORM Body Treatment with TriHex Technology is high value for high price point You can’t go wrong with the trusty Avené Cicalfate+ Restorative Protective Cream The Westman Atelier Vital Skincare Complexion Drops are the perfect no-makeup makeup base Jones Road is always a winner Add to Queue: Outer Banks Casey was influenced by Olivia Chatfield to get the Charlotte Tilbury Hollywood Contour Wand The Mid-Day Squares are a real treat Protect your skin from “car sun” with these window shades Love Casey and Danielle? Join Garbage World! Stay up to date with us on Twitter, Facebook, and Instagram at @LemonadaMedia. Joining Lemonada Premium is a great way to support our show and get bonus content. Subscribe today at bit.ly/lemonadapremium. Click this link for a list of current sponsors and discount codes for this show and all Lemonada shows: lemonadamedia.com/sponsorsSee omnystudio.com/listener for privacy information.

In part one of this two-part series, Dr. Jeff Ratliff and Dr. Brin E. Freund discuss the incidence of acute symptomatic seizures during CAR T-cell therapy.  Show reference:  https://www.neurology.org/doi/10.1212/WNL.0000000000213535   

Dr. John Sweetenham and Dr. Marc Braunstein highlight top research on hematologic malignancies from the 2025 ASCO Annual Meeting, including abstracts on newly diagnosed chronic phase CML, relapsed B-cell lymphoma, and multiple myeloma. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. On today's episode, we'll be discussing promising advances in newly diagnosed chronic phase CML, relapsed B-cell lymphoma, multiple myeloma, and other hematologic malignancies that were presented at the 2025 ASCO Annual Meeting. Joining me for this discussion is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode.  Marc, there were some great studies in the heme space at this year's Annual Meeting, and it's great to have you back on the podcast to highlight some of these advances. Dr. Marc Braunstein: Yes, I agree, John, and thank you so much for inviting me again. It's great to be here.  Dr. John Sweetenham: Let's start out with Abstract 6501. This was a study that reported on the primary endpoint results of the phase 3B ASC4START trial, which assessed asciminib versus nilotinib in newly diagnosed chronic phase CML. And the primary endpoint of this, as you know, was time to treatment discontinuation because of adverse events. Can you give us your insights into this study? Dr. Marc Braunstein: Absolutely. So, like you mentioned, you know, asciminib is an allosteric inhibitor of the BCR-ABL kinase that has activity in CML, and that includes patients with the T315I mutation that confers resistance to first- and second-generation TKIs. So, the ASC4FIRST study, which was published last year in the New England Journal of Medicine, showed superior efficacy of asciminib compared to investigator-selected first- or second-generation TKIs, actually leading to the FDA approval of asciminib in first-line CML. So, the authors of that study presented data at this year's ASCO meeting from the phase 3 ASC4START comparing safety and time to discontinuation due to adverse events of asciminib versus nilotinib, a second-generation TKI. So, 568 patients with newly diagnosed CML were randomized one-to-one to once-daily asciminib or twice-daily nilotinib. So, at a median follow-up of 9.7 months, about 11% in the asciminib group and 17% in the nilotinib group discontinued treatment, with significantly fewer discontinuations with asciminib due to adverse events. There was also a secondary endpoint of major molecular response, which was also better with asciminib. For example, the MR 4.5, which is a deep response, was 2.5% versus 0.4% favoring asciminib by week 12. So, I think in conclusion, these results build on the ASC4FIRST study, making the case for the superior safety and efficacy of asciminib versus other first- or second-generation TKIs in newly diagnosed CML. Dr. John Sweetenham: Thanks, Marc. Do you think this is going to change practice? Dr. Marc Braunstein: I think so. I think there are still some questions to be answered, such as what resistance mutations occur after first-line treatment with asciminib. But I think the sum of these studies really make the case for using asciminib upfront in CML. Dr. John Sweetenham: Okay, great. Thank you. And let's move on to our second abstract. This was Abstract 7015 and was reported from Mass General Hospital. And this was a study in patients with relapsed and refractory diffuse large B-cell lymphoma and reported the 2-year results of the so-called STARGLO study. This is a comparison of glofitamab, a T-cell engaging bispecific antibody, with gemcitabine and oxaliplatin in this group of patients. Can you tell us a little bit about your impressions of this study? Dr. Marc Braunstein: Absolutely. So just for background, the treatment landscape for relapsed/refractory large B-cell lymphoma is expanding, now with two bispecific antibodies targeting CD20 that are approved after two or more lines of therapy. Among these, glofitamab was approved in 2023 based on phase 2 data showing an objective response rate of 52%, with 39% complete responses in relapsed/refractory large B-cell lymphoma patients after a median of three prior lines of therapy. Distinguishing glofitamab from epcoritamab, the other approved bispecific, glofitamab was given for 12 cycles and then stopped. Additionally, when combined with gemcitabine and oxaliplatin in the phase 3 STARGLO study, there was significantly improved overall survival compared to rituximab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory large B-cell lymphoma patients at a median follow-up of 11 months.  The authors of that study published last year in Lancet now present at ASCO this year the 2-year follow-up of the STARGLO study. Two hundred and seventy-four patients with a median of one prior line of therapy were randomized two-to-one to glofitamab plus GemOx versus rituximab plus GemOx, with the primary endpoint of overall survival. Here, the median overall survival was not reached versus 13.5 months, with a median PFS also significantly improved at about 14 months versus 4 months in the control. CRS of note in the glofitamab arm was mostly grade 1 or 2, with only about 2.3% grade 3 events. And three of the four patients had grade 1 or 2 neurotoxicity. So, John, putting this into context, I think it's encouraging that we now have randomized data showing the superiority of a bispecific plus chemotherapy over rituximab plus chemotherapy in transplant-ineligible patients. And while only 8% of the patients in the STARGLO study had prior anti-CD19 CAR T-cell therapy, I think this regimen could be considered in those patients who are ineligible for transplant or CAR T-cell therapy. Dr. John Sweetenham: Yeah, I agree. I think a couple of other compelling numbers to me were the fact that around 55% of these patients were alive at 2 years in the group who'd received glofitamab, and that almost 90% of those having that arm of the study who had a CR at the end of treatment were alive at 12 months. So, clearly, it's an active agent and also a kind of great off-the-shelf fixed-duration alternative in these relapsed and refractory patients. Dr. Marc Braunstein: I agree, and I would also note that the phase 3 SKYGLO study is looking at glofitamab plus Pola-R-CHP versus Pola-R-CHP alone. So, we may even be using these eventually in the first-line setting. Dr. John Sweetenham: Absolutely. Let's stay on the theme of diffuse large B-cell lymphoma and look at one other abstract in that space, which was Abstract 7000. This was a study from the HOVON group in the Netherlands, which looked at the prospective validation of end-of-treatment circulating tumor DNA in the context of a national randomized trial. What are your thoughts on this? Dr. Marc Braunstein: So, non-invasive liquid biopsies to detect and monitor cancers via circulating tumor-derived DNA or ctDNA, you know, is really emerging as a valuable tool in both solid and liquid tumors to understand disease biology, and also for drug development. So, to date, the most established application of ctDNA in lymphoma, I would say, is really for monitoring of minimal residual disease. So, in this correlative study by Steven Wang and colleagues in the HOVON group, they evaluated the prognostic significance of MRD status as assessed by ctDNA following first-line treatment with curative intent with either R-CHOP or dose-adjusted R-EPOCH. At the end of treatment, encouragingly, 76% of patients were MRD-negative, and 24% were MRD-positive. Now, of note, MRD-positive status at the end of treatment predicted inferior progression-free survival at 2 years, with only 28% of patients who are MRD-positive being progression-free versus 88% who are MRD-negative. And in fact, all the patients who failed to achieve a complete response after first-line treatment and were MRD-positive ultimately relapsed. So, circulating tumor cells are rarely found in large B-cell lymphomas, and so this study really builds on accumulating data that ctDNA has clinical value to detect residual disease with a non-invasive approach. So, there are many implications of how we could potentially use this to detect early signs of relapse, to potentially escalate treatment for consolidation if patients remain MRD-positive. So, I think this will eventually become utilized in clinical practice. Dr. John Sweetenham: Yeah, I agree. I think it's interesting that it provided an independent assessment of response, which was independent, in fact, of the results of PET-CT scanning and so on, which I think was very interesting to me. And the authors of the abstract actually commented in their presentation that they think this should be integrated as part of the standard response assessment now for patients with large B-cell lymphoma. Would you agree with that? Dr. Marc Braunstein: I would. For one thing, it allows repeated sampling. It's a non-invasive approach; it doesn't necessarily require a bone marrow biopsy, and it may have more sensitivity than conventional response measures. So, I think having a standardized system to assess ctDNA will be helpful, and definitely, I think this will be a valuable biomarker of disease response. Dr. John Sweetenham: Okay, great. Thanks. We're going to change gear again now, and we're going to highlight two abstracts in the multiple myeloma space. The first one of these is Abstract 7507. And this abstract reported on the long-term results of the CARTITUDE study for patients with relapsed and refractory multiple myeloma. What are your comments on this presentation? Dr. Marc Braunstein: So, this study actually got a lot of press, and I've already had multiple patients asking me about CAR T-cells as a result. Just as some background, CAR T-cells targeting BCMA, which is pretty much universally expressed on malignant plasma cells in myeloma, have really shown remarkable responses, especially in heavily pretreated patients, showing superior progression-free survival in both later and earlier phases of the disease, including in randomized studies in patients with second-line or beyond. So, the CARTITUDE-1 was really the original Phase 1/2 study of ciltacabtagene autoleucel, one of the two approved anti-BCMA CAR T-cell products, which was investigated in patients with a median of six to seven prior lines of therapy. So, these were patients who were pretty heavily pretreated. So, in the study presented by Voorhees at this year's ASCO meeting, this was the long-term follow-up at a median of 5 years from the one-time CAR infusion in these patients with a median of five prior lines of therapy. And remarkably, of the 97 patients, 33% remained progression-free at 5 years plus, without needing any further myeloma treatment during that time. And among those 33% of patients, 23% had high-risk cytogenetics, which we know are notoriously difficult to achieve responses in. What was interesting that they presented as correlative studies was there were some biomarkers that were distinguishing the patients who had the long PFS, including enrichment of more naive T-cells in the product, lower neutrophil-to-T-cell ratio, higher hemoglobin and platelets at baseline, and higher CAR T-cell levels relative to soluble BCMA levels. And the fact that they reported a median overall survival of 61 months in these really heavily pretreated patients, I think these data are impressive. I think we're going to continue to be using CAR T even earlier in the disease status than fifth or sixth line, as it was studied in CARTITUDE-1. There are even ongoing studies looking at first-line treatment with CAR T-cells. Dr. John Sweetenham: So, do you think that those 33% of patients who are disease-free at 5 years, do you think any of those are cured?  Dr. Marc Braunstein: That was one of the headlines in the press. I think if we're going to discuss things like "operational cures," where we're transforming myeloma into really a chronic disease, where patients can live practically a normal life expectancy, I think the measure of 5 years, especially in this population that was explored in CARTITUDE-1, I think we can call that close to a cure. Dr. John Sweetenham: Okay. Well, thank you. Exciting data, for sure. We're going to conclude today with another abstract in the multiple myeloma space. And this was Abstract 7500, which looked at an MRD, minimal residual disease-driven strategy following induction and transplant-eligible newly diagnosed multiple myeloma patients and reported on the primary endpoints of the phase 3 MIDAS trial. Can you walk us through this one, Marc? Dr. Marc Braunstein: Absolutely. It is a bit more complicated than the prior one we discussed because this is a randomized study with four arms. So, I'll start by saying that anti-CD38-based quadruplet regimens continue to show superior outcomes in both transplant-eligible and -ineligible newly diagnosed multiple myeloma patients. The MIDAS study mentioned is an open-label phase 3 trial with four arms in transplant-eligible newly diagnosed myeloma patients.  And initially, these patients were all treated with quadruplet therapy with the anti-CD38 antibody isatuximab combined with carfilzomib, lenalidomide, and dexamethasone in 718 newly diagnosed myeloma patients. So, they received the quadruplet regimen for six cycles and then were randomized based on their MRD status at 10 to the negative fifth following six cycles of induction. And that first randomization, if they were MRD-negative, was to either consolidation with six more cycles of the quadruplet regimen or transplant, autologous transplant, plus two cycles additionally of the quadruplet regimen. And both arms were followed by lenalidomide maintenance. The primary endpoint was MRD negativity at 10 to the negative sixth prior to entering the lenalidomide maintenance component. And in addition, the patients who were MRD-positive after induction were randomized to transplant plus two cycles of consolidation or a tandem autologous transplant. So, the median follow-up of the study was about 16 months, and the pre-maintenance rate of MRD negativity was high, between 84 to 86% between the two arms who were MRD-negative, which was not significantly different. And as far as the 233 patients who were MRD-positive, the pre-maintenance MRD negativity was also not significantly different at 40% for those who received autologous transplant, and 32% who received a tandem transplant. So, there's a lot of debate in the myeloma field about the evolving role of autologous transplant and whether transplant still plays a significant role in patients who are either MRD-negative after induction or who have deep remissions and are of standard risk. So, I think these data suggest that patients who are MRD-negative after induction with a quadruplet regimen studied here, which was Isa-KRd, plus consolidation, may possibly be able to forego consolidation with autologous transplant. And likewise, for those patients who are MRD-positive after induction, tandem transplant didn't seem to provide much of a benefit compared to single transplant, which is consistent with prior studies such as the StaMINA study. Dr. John Sweetenham: So, where do you think this leaves us, Marc? Are we going to need more studies before we have any definitive guidance on whether an autologous transplant is still appropriate for those patients who are MRD-negative? Dr. Marc Braunstein: Well, as clinicians, we want to do what's best for our patient. And in myeloma, the best we can do is to get as deep remissions as possible, meaning MRD negativity. And so, I think it's clear from the MIDAS study and others that quadruplet regimens provide the deepest remissions when given upfront. We can debate the role of autologous transplant. I think certainly the role of tandem autologous transplant is fading. But as far as a single autologous transplant as consolidation, I think it's reasonable as a goal to try to achieve MRD negativity after the transplant, especially for patients who remain MRD-positive after induction. Dr. John Sweetenham: Okay, great. Marc, thanks as always for sharing your insights on the heme malignancies studies from the ASCO meeting this year and for joining us on the ASCO Daily News Podcast. Always appreciate hearing your thoughtful and balanced input on these. Dr. Marc Braunstein: My pleasure. Thank you, John. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   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. 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.   Find out more about today's guest:  Dr. John Sweetenham Dr. Marc Braunstein   @docbraunstein     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp  Speakers' Bureau: Janssen Oncology  Research Funding (Institution): Janssen, Celgene/BMS

Ken and Anthony tell you the three worst words you can hear in the summer and talk through Lima abandoning the game.

The three worst words of summer: Cart path only+Mary Kay Cabot: Shedeur speeding is not a great look in midst of 4-way QB battle+What's the best path at QB to ensure Stefanski, Berry keep their jobs?

Dr. Jeff Ratliff talks with Dr. Brin E. Freund about the evaluated incidence and risk factors for acute symptomatic seizures during CAR T-cell therapy. Read the related article in Neurology®.  Disclosures can be found at Neurology.org. 

In today's episode, we had the pleasure of speaking with Alexey Danilov, MD, PhD, about current challenges and emerging treatment approaches for the management of leukemia and lymphoma that were published in a manuscript based on proceedings from the inaugural Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Conference. Dr Danilov is the Marianne and Gerhard Pinkus Professor of Early Clinical Therapeutics, medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, co-director of the Toni Stephenson Lymphoma Center, and a professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California. In our exclusive interview, Dr Danilov highlighted recent advances and controversies in the treatment of select patients with hematologic malignancies. He noted chemotherapy-free regimens that are shifting treatment paradigms in mantle cell lymphoma, preferred and emerging BTK inhibitors for the management of chronic lymphocytic leukemia, and the evolution of CD19-directed CAR T-cell therapies for diffuse large B-cell lymphoma. Dr Danilov concluded by taking a forward glance at future developments like BTK degraders and novel CAR T-cell therapy targets.

Blood editor Dr. Laurie Sehn discusses the topic of "Aggressive non-Hodgkin lymphoma: defining and managing high-risk subsets" featuring Drs. Mark Roschewski, Grzegorz Nowakowski, and Neha Mehta-Shah, who each contributed to the articles featured in the review series on high-risk aggressive lymphoma.See the full review series on high risk lymphoma in volume 144, issue 25 of Blood.

In this episode of The Influence Factor, Alessandro Bogliari chats with Alanah Joseph, Head of Creator Partnerships at HubSpot. Alanah shares how creator partnerships are evolving, why community is key in podcasting, and strategies to grow and monetize a podcast. From networking and consistent publishing to leveraging newsletters, she offers practical insights for creators and brands alike.

Send us a textThis episode we sit down with Dr. Akhavan, Physician Scientist at The University of Kansas Cancer Center, to dive deep into the promising world of CAR T-cell therapy. Dr. Akhavan breaks down how this innovative treatment is being applied in the brain cancer space, what patients and families need to understand about its potential and limitations, and why quality of life remains a critical part of the conversation. Whether you're newly navigating a diagnosis or seeking new hope in treatment options, this episode is packed with valuable insight, empathy, and education.Support the showRare Enough is a podcast powered by Head for the Cure, sharing real stories of resilience, hope, and community from those facing brain tumors and the people who walk beside them. Subscribe, listen, and share, because every story matters, and no one should face brain cancer alone. Follow on Instagram @RareEnoughPodcast Learn more at BrainsfortheCure.org

If you're not backing us yet, head on over to our Patreon. A contribution of at least $5 a month will[...]

One of my clients just had a $63,000 launch with an almost 9% conversion rate - but honestly? The money is the least exciting part of this story. What she really achieved was proving to her nervous system that success doesn't require chaos. I work with a lot of women who have been responsible for others from a young age - incredible problem-solvers who thrive in chaos. In business, this often translates to overcomplicating everything because complexity feels safer than simplicity. But what happened when we focused her entire launch strategy on ONE thing - her waitlist - changed everything. In this episode, I'm breaking down exactly how this waitlist strategy works, why 85% of her sales came from focused effort, and the nervous system breakthrough that was more valuable than any dollar amount.In this episode, I share:

The microbiome is emerging as a key player in the effectiveness of CAR-T therapy, and today, Dr. Melody Smith, Assistant Professor of Medicine at Stanford University, sheds light on this fascinating intersection. Join us as we explore how advancements in CAR T-cell therapy are reshaping patient demographics and treatment approaches. Dr. Smith will discuss the implications of genetic engineering techniques like CRISPR, the importance of a multidisciplinary treatment strategy, and the role of antibiotic stewardship in optimizing outcomes. With insights into innovative therapies and ongoing clinical trials, this conversation promises to deepen your understanding of CAR-T therapy and its complexities, offering a glimpse into the future of cancer treatment. Read Transcription CME Information: https://stanford.cloud-cme.com/medcastepisode107 Claim CE: https://stanford.cloud-cme.com/Form.aspx?FormID=3392

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. Sarepta Therapeutics faced a drop in shares due to a second death from acute liver failure in a patient receiving their DMD gene therapy. On the other hand, Sage Therapeutics had a positive outcome with a $795 million acquisition by Supernus, surpassing a bid from Biogen. Meanwhile, Lilly saw promising results in a phase I study of their amylin/tirzepatide combo for weight loss. J&J's dual-targeting CAR T-cell therapy showed an 80% complete response rate in early lymphoma studies, demonstrating potential in the field. In addition, Intellia Therapeutics is dedicated to developing potentially curative genome editing treatments for severe diseases, showing promise for future advancements in healthcare.

An expert panel highlights key presentations in multiplemyeloma, lymphoma, and other hematologic malignancies at the 2025 ASCO Annual Meeting.CancerNetwork®, in collaboration with The American Societyfor Transplantation and Cellular Therapy (ASTCT), organized an X Space hosted by Rahul Banerjee, MD, FACP; Taha Al-Juhaishi, MD; and Muhammad Salman Faisal, MD. This expert panel convened to discuss key presentations and abstracts of interest at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting featuring noteworthy developments in modalities like CAR T-cell therapy and transplantation across multiple myeloma, lymphoma, and other disease types.Banerjee is an assistant professor in the Clinical Research Division at the Fred Hutchinson Cancer Center in Seattle, Washington. Al-Juhaishi is the associate director of the Hematopoietic Stem Cell Transplantation and Cell Therapy Program at Oklahoma University Health Stephenson Cancer Center and an assistant professor of medicine at the University of Oklahoma College of Medicine. Faisal is a hematologist/oncologist at Oklahoma University HealthStephenson Cancer Center and serves as an ambassador for ASCO.The group highlighted several late-breaking abstracts,plenary sessions, and poster presentations focused on significant clinical trial data and other findings across the hematologic oncology landscape. Topics of interest included the following:Phase 1b/2 CARTITUDE-1 trial (NCT03548207,NCT05201781)1Long-term follow-up showed that approximately one-third(33%; n = 32) of patients with relapsed/refractory multiple myeloma maintained progression-free status for at least 5 years following a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti). An equal likelihood of progression-free survival occurred in patients with high-risk cytogenetics or extramedullary plasmacytomas.With a median follow-up of 61.3 months, the median overall survival (OS) with cilta-cel was 60.7 months (95% CI, 41.9-notevaluable [NE]). Real-world axicabtagene ciloleucel (axi-cel; Yescarta) use2Across inpatient and outpatient treatment settings, safety and efficacy outcomes were comparable for patients who received axi-cel for relapsed/refractory large B-cell lymphoma.Multivariate analysis showed no associations between intended care setting and cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.Investigators noted that these real-world data support the consideration of axi-cel in appropriate outpatient settings.Phase 1b/2 NEXICART-2 trial (NCT06097832)3Investigators assessed NXC-201, a sterically optimized CAR T construct, as a treatment for patients with relapsed/refractory light chain amyloidosis, a population with no FDA-approved options.Among 12 patients who received the agent at 450x 106 cells, 100% achieved rapid and deep hematologic responses at a median time to first and best response of 7 and 26 days, respectively. With a median follow-up of 121 days (range, 29-289), no hematologic relapses or progression had occurred.References1.     Voorhees P, Martin T, Lin Y, et al. Long-term (≥5 year) remission and survival after treatment with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2025;43(suppl 16):7507. doi: 10.1200/JCO.2025.43.16_suppl.75072.     Furqan F, Hemmer M, Tees M, et al. Trends and outcomes by inpatient and outpatient infusion of axicabtagene ciloleucel (axi-cel) in the US for patients (pts) with relapsed/refractory large B-celllymphoma (R/R LBCL). J Clin Oncol. 2025;43(suppl 16):7023. doi:10.1200/JCO.2025.43.16_suppl.70233.     Landau H, Hughes C, Rosenberg A, et al. Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, Nxc-201. J Clin Oncol. 2025;43(suppl 16):7508.doi:10.1200/JCO.2025.43.16_suppl.7508

This year's Randy Shaver Cancer Research and Community Fund's Angel Award recipient talks about his cutting edge work with Natural Killer Cell immunotherapy, CAR-T cell immunotherapy and the future of genome engineering in new therapies for treating cancer.Here how he became interested in creating new ways to look at knocking down cancer, his background as a youth growing up in rural Minnesota and trending as one of the most talked about researchers at the University of MN.

A Cirrus with fluctuating fuel flow, de-injecting an engine, and fear of overhaul are on tap for this episode. Email podcasts@aopa.org for a chance to get on the show. Join the world's largest aviation community at aopa.org/join Full notes below: Joe has a Maule with a 540 engine in it. The company has a mod to turn the engine to a carbureted version and he's wondering about the legality of something like that. Paul said it happens in the 210 market. Whether it's a good idea is another issue, the hosts say. Joe is unable to run autofuel is the injected version, which is why he's interested in it. Colleen said she'd rather have an injected engine than run mogas.   David wonders how perspective owners are so afraid of TBO. He has a 182 with an engine that's nearly at TBO, and people who contact him are afraid of the high time. The hosts discuss strategies for buyers who may be looking at airplanes with engines at TBO. Assuming the engine is running well, a new owner can fly it on that “borrowed time” while they learn and enjoy the airplane. Alternatively, if the engine truly needs to be overhauled, the time down is obviously a concern for a new owner. Mike said he thinks it's best to buy an airplane with a run-out engine. The price has been discounted for the cost of the engine, the seller is motivated, and worst case you have to overhaul it soon. And every hour and year that you don't have to overhaul it is “free.” And when it does come time to do the overhaul, you get to do it to your spec.   Shalom has a Cirrus that isn't behaving. If he sets the mixture at lean of peak, the fuel flows start to fluctuate. A few minutes later, it will drop off sharply, and then back quickly. The manifold pressure and rpm stay pretty consistent. He's changed the fuel pump and the spider. Nothing has helped. Mike said if there's a constriction in the fuel line between the fuel control unit and the manifold, it can cause oscillating fuel flow and lower flows.

durée : 00:09:44 - L'invité de 7h50 du week-end - Claire Bernardi, directrice du Musée de l'Orangerie et co-commissaire de l'exposition “Dans le Flou, une autre vision de l'art de 1945 à nos jours” jusqu'au 18 août au Musée de l'Orangerie. Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

Broadcast from KSQD, Santa Cruz on 6-12-2025: Dr. Dawn opens with alarming news about NIH budget cuts devastating cancer research just as breakthrough CAR-T cell therapy shows promise for gastrointestinal cancers. This personalized immunotherapy extracts patients' T cells, engineers them to target specific cancer antigens, and makes them essentially immortal before reinfusion. While previously successful only for blood cancers like leukemia and lymphoma, researchers achieved tumor shrinkage in 25% of solid GI tumor patients. However, devastating layoffs forced removal of two patients from trials due to staff shortages and supply chain disruptions. Dr. Dawn emphasizes how pregnancy can worsen hidden cancers due to immune suppression, explaining why aggressive metastasized cancers often appear shortly after childbirth. Dr. Dawn takes a call from Bob about concerning forehead growths his dermatologist examined. She speculates they're likely seborrheic keratoses - benign, stuck-on appearing growths common in sun-exposed areas that look like crumpled brown paper "spit-wads". These aging-related changes are harmless and can even be picked off, though she warns against repeatedly traumatizing any skin area as this increases cancer risk through accumulated DNA damage. She explains how repetitive trauma in occupational settings creates statistically higher cancer risks, comparing it to filling a bingo card of cellular errors. She addresses an email about Joe Tippens' cancer cure protocol involving fenbendazole, an anti-parasitic drug. Dr. Dawn explains this viral social media phenomenon began when Tippens claimed his lung cancer was cured by fenbendazole, but he was simultaneously receiving Keytruda immunotherapy at MD Anderson. The story spread rapidly in South Korea, causing pharmacy shortages. Unvalidated internet health information can spread dangerously. Dr. Dawn compares it to old-fashioned medicine show scams. trend Dr. Dawn warns about a recent vitamin B6 toxicity misdiagnosis trend affecting her patients who were told they had dangerous levels of B6 despite lacking neuropathy symptoms. Accuracy requires fasting 12 hours before blood draws, otherwise creating false elevations from recent vitamin consumption. More critically, she alerts listeners about biotin(Vitamin B7) interference with laboratory tests using biotin-streptavidin techniques. High-dose biotin supplements are often used in hair and nail health growth formulas. This can falsely alter tests for thyroid hormones, vitamin D, sex hormones, cortisol and dangerously, troponin levels that diagnose heart attacks. This could lead to missed myocardial infarctions in emergency rooms, potentially causing fatal outcomes. Dr. Dawn takes a call from Richard seeking information about a previous radio program guest. She guides him to use on-line resources at ksqd.org to find program details, pivoting into praise for libraries as community centers offering far more than internet access. She emphasizes libraries provide serendipitous discovery that algorithms can't match, encouraging people to explore their local library systems for events, historical collections, and personal assistance from knowledgeable librarians eager to help visitors navigate both physical and digital resources. She discusses the concerning trend of giving melatonin to children, calling it "the Grinch that stole children's bedtime." While used prescription-only for severe developmental disorders in Denmark and EU countries, American children receive melatonin gummies regularly, with one in five preteens using it occasionally. Dr. Dawn explains melatonin is a hormone affecting pancreas, heart, fat tissue, and reproductive organs still developing in children. Supplemental doses create blood levels 10 times higher than natural peaks, representing an uncontrolled medical experiment on developing brains and bodies. Poison control calls for melatonin ingestion increased 530% between 2012-2021, with one tragic case involving a three-month-old death where 20 melatonin bottles were found in the home. Dr. Dawn concludes by debunking food expiration date myths, explaining that Americans waste a third of food ($7 billion annually) due to misunderstanding labels. Most shelf-stable foods simply degrade in quality rather than becoming dangerous after printed dates. She notes acidic dairy products like yogurt resist bacterial contamination due to protective bacteria,and even surface mold can be scraped off safely. However, she emphasizes trusting expiration dates on lunch meats and deli products, which pose real listeria risks when stored improperly. California will soon simplify labeling laws to reduce confusion between quality and safety dates.

We start off with some good old spaceweather news, which leads into a discussion of the Earth's rapidly weakening magnetic field and the possibility of a polarity flip. We then move on to some discussion of further observations on the construction of pyramids and new things we learned in our recent trip in Egypt.In the second half of the show, we talk about the amazing cart ruts we visited in the Phrygian Valley in Turkey. We show lots of pictures and video, and discuss and discard multiple hypotheses on what they are and how they were formed.Join us, Ben from UnchartedX, Adam Young, and Karoly Poka for an afternoon at The Metropolitan Museum of Art in New York where we will peruse their collection of Ancient Egyptian artifacts, then we will move to the Explorer's Club for dinner and presentations from us and Ben!https://eveningattheexplorersclub.eventbrite.com/Join our Patreon, support the show, get extra content and early access!https://www.patreon.com/brothersoftheserpentSupport the show with a paypal donation:https://paypal.me/snakebros

Drs. Lipsky and Allan discuss the emerging role of immunotherapy in the management of patients with CLL, including CAR T-cell therapy and bispecific antibodies.

In this week's episode, we' ll learn about how TET3 has a key role in GVHD. In mice, a deficiency of Tet3 in donor T cells inhibited pathogenic immunoglobulin class switching and suppressed lung fibrosis. Accordingly, TET3 may be a new therapeutic target in chronic GVHD. After that: rilzabrutinib, a BTK inhibitor for ITP. In a randomized, placebo-controlled trial, treatment produced rapid and durable platelet responses, with acceptable safety, in adults with immune thrombocytopenia who had failed multiple previous therapies. Finally: exploring pre-TCR surface expression patterns in T-cell ALL. Co-inhibition of the interleukin-7 receptor and pre-T cell receptor pathways may play a therapeutic role for a subset of T-lymphoblastic leukemias.Featured Articles: Deficiency of T follicular helper cell Tet3 DNA demethylation inhibits pathogenic IgG2c class switching and chronic GVHDSafety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 studySurface pTα expression predicts LCK activation and preclinical synergy of LCK and JAK coinhibition in adult T-ALL

Uma Borate, MBBS, MS, The Ohio State University, Cleveland, OH Recorded on May 27, 2025 Uma Borate, MBBS, MS Associate Professor, Division of Hematology Acute Leukemia Clinical Research Disease Group Leader The Ohio State University Cleveland, OH What's changing in acute myeloid leukemia (AML)? Join Dr. Uma Borate from The Ohio State University in Columbus, Ohio, as she dives into emerging breakthroughs in AML biology, including molecular drivers, menin inhibitors, and the challenges of developing bispecifics and CAR T-cell therapies. She also shares updates from the LLS Beat AML® Master Clinical Trial and ongoing clinical trials, and reflects on the evolving treatment landscape across age groups. Don't miss this dynamic conversation packed with expertise and hope for the future of AML!

Pole Vault U. Don't take that nap. State of Beverages report. Soda stats. Moving sidewalks might be on the way out. High school experiences. Jokes with Sean. Bacon news. Winner! Trademark wars. Pizza Vodka. Bar tabs.

This week Shauna and Dan try not to upset the apple cart. Bonus: The USA's earliest pen pals, wizardly cats, and Gudrun Lauret's disruptive creators (or possibly creative disruptors) It's free to join our Patreon, patreon.com/bunnytrailspod On our Patreon you have direct access to reach Shauna and Dan, plus join our weekly chats and polls. Paid tiers have even more perks, like early access and name recognition on the show. So join us on Patreon! patreon.com/bunnytrailspod Shownotes are always available on our website, bunnytrailspod.com Copyright 2025 by The Readiness Corner, LLC - All Rights Reserved  

In this hilarious and unfiltered episode, Donna and Brittney Boo are joined by returning guest and cart cutie Nathalie for a deep dive into the wild world of the beverage cart. It's time for confessions, cocktails, and the colorful cast of characters they encounter every week on the course.Brought to you by our favorite beverage cart experts (and cuties), Brittney Boo & Nathalie, this episode covers:*The wildest moments from the Kachina Men's Invitational at Alta Mesa*Best customer of the week, worst attitude, and a few touching moments of kindness*The top 3 most-ordered drinks right now*Donna's new favorite summer cocktail*What your drink says about your golf game (you'll either laugh—or feel very seen)*Cart-side fashion breakdowns: who's nailing the look, who's missing the mark, and a few surprises that somehow worked*A quick tip from Donna on how to balance style and function on the courseThe players who show up to slay, not score—and why we love them for itWe wrap up with Cart Confessionals (yes, they're juicy!) and break down the formats from the Alta Mesa Member-Guest: scrambles, best balls, Calcutta, horse race, and the classic ham and egg strategy.This episode is all fun, flavor, and fairway chaos—a true look into the day in the life of the beverage cart crew.Big thanks to our amazing listeners—old and new—for tuning in!Please keep sharing Golf Party Live with your golf girlfriends (and guy friends too).And we'd love to hear from you—what's your go-to cocktail on the course or at the 19th hole? Drop us a message or tag us in your favorite drink pics!

In this episode, Heather and Matthew welcome Dr. Leonardo Ferreira, Assistant Professor at the Medical University of South Carolina and cofounder of Torpedo Bio. Leo shares how his team at Torpedo Bio  is working to develop safe and effective cellular immunotherapy for solid tumors. We have an exciting conversation on the promise of CAR-T therapy, the challenges life sciences startups face, and how federal research funding impacts innovation. Tune in to hear how Torpedo Bio is pushing the boundaries of cancer treatment!

We start off with some good old spaceweather news, which leads into a discussion of the earth's rapidly weakening magnetic field and the possibility of a polarity flip. We then move on to some discussion of further observations on the construction of pyramids and new things we learned in our recent trip in Egypt. In the second half of the show, we talk about the amazing cart ruts we visited in the Phrygian Valley in Turkey. We show lots of pictures and video, and discuss and discard multiple hypotheses on what they are and how they were formed.   Join us, Ben from UnchartedX, Adam Young, and Karoly Poka for an afternoon at The Metropolitan Museum of Art in New York where we will peruse their collection of Ancient Egyptian artifacts, then we will move to the Explorer's Club for dinner and presentations from us and Ben! https://eveningattheexplorersclub.eventbrite.com/ Join our Patreon, support the show, get extra content and early access! https://www.patreon.com/brothersoftheserpent Support the show with a paypal donation: https://paypal.me/snakebros   Chapters 00:00 Welcome to Brothers of the Serpent 02:01 Space Weather News 05:32 Earth's Magnetic Field Dynamics 10:05 Geomagnetic Excursions and Their Implications 15:49 Magnetic Field Weakening and Its Consequences 20:08 Mars, Venus, and Planetary Magnetic Fields 24:22 Life on Other Planets: The Case of Europa 28:08 Life in Extreme Environments 29:51 Theoretical Life Forms and Energy 31:21 Science Fiction Inspirations 33:35 Podcast Reflections and Communication Barriers 34:35 Debating Ancient Structures 37:43 Pyramid Construction Insights 39:20 The Anatomy of Pyramids 42:30 Theories on Pyramid Design 50:30 Mythology and Historical Interpretation 58:24 Exploring the Met and Event Details 59:08 The Mystery of Cart Ruts 01:01:03 Colonial Cart Ruts: A Historical Perspective 01:03:20 Investigating Turkish Cart Ruts 01:06:03 Analyzing the Characteristics of Ruts 01:09:12 Theories on Rut Formation 01:12:32 Erosion and Its Impact on Ruts 01:15:58 The Case for Hand-Carved Ruts 01:19:20 Challenging Conventional Explanations 01:27:59 Concluding Thoughts on Cart Ruts 01:29:25 Exploring the Mechanics of Ruts 01:36:00 Drone Footage Insights 01:43:11 The Mystery of Disappearing Ruts 01:50:06 Theories and Speculations on Cart Ruts

These lectures will explore two Arthurian romances, Chretien de Troyes' Knight of the Cart, and the Cistercian text we know as The Quest of the Holy Grail, through the lens of Catholic teaching on redemption, divine grace, and the pursuit of virtue.

Episode 237 This episode has stories about lost items, telepathy, Korea, beverage carts, Sri Lanka and a backpack nazi. Contact... flywithbetty@gmail.com The Telepathy Tapes Ravens Cup Coffee and Art Gallery, La Conner, WA Let's Talk Off Camera My website Patreon Instagram:Bettyinthesky Twitter: Skybetty My Amazon page

This month, the gals are visited by Cassidy Liston from Drinking the Koolaid Podcast to discuss gull shrieking, mystery man meats, angel eggs, red-wing red flags, crystal-encrusted corpses, and a suspiciously bound book. Tune in for May's episode of Gossip at the Corpse Cart! For a full list of show sponsors, visit https://wineandcrimepodcast.com/sponsors. To advertise on Wine & Crime, please email ad-sales@libsyn.com or go to advertising.libsyn.com/winecrime.