Podcasts about velcade

Guest Dr. Sundar Jagannath and host Dr. Davide Soldato discuss JCO article "Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma," and the efficacy of CAR-T cell therapy in patients with heavily pretreated RRMM (relapsed/refractory multiple myeloma). TRANSCRIPT Dr. Davide Soldato: Hello and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, medical oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author, Professor Sundar Jagannath, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and the Tisch Cancer Institute. He also serves as Network Director for the Center of Excellence for Multiple Myeloma, and he is an internationally recognized expert in the field of multiple myeloma. Today, we will be discussing the article titled, "Long-Term Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma." Thank you for speaking with us, Professor Jagannath. Dr. Sundar Jagannath: Thank you for having me, Dr. Davide Soldato. It is a pleasure to be here. JCO is a highly recognized journal among the oncologists, so I am very happy and privileged to be here today. Dr. Davide Soldato: Thank you so much for being with us. So, I wanted to start a little bit with the rationale of the study and the population that was included in the study. So, the trial that we are discussing, CARTITUDE-1, was already published before, and we observed very good results with a single infusion of cilta-cel. So we had previously reported a median progression-free survival of 30 months, and median overall survival was not reached. So, I just wanted to ask you if you could guide us a little bit into the population that was included in the study and also explain a little bit to our listeners what is the drug that we are discussing, cilta-cel. Dr. Sundar Jagannath: It is a CAR T-cell. This is a patient's own lymphocytes, which goes through apheresis and is sent to the company, where they modify it and introduce the B cell receptor. In this case, you know, there is a heavy chain gene receptor for the BCMA, and in cilta-cel, there are actually two receptor sites on each molecule, or there are two binding domains on each receptor molecule. So, it is considered to be quite efficacious. As you reported, the earlier results that the patients who participated, 97% of the patient responded. Now, you asked about the patients who participated in the clinical trial. This clinical trial was conducted between July of 2018 and October of 2019. At that time, this was a phase 1b/phase 2 trial, and the whole idea was to take patients who had relapsed all the available treatment regimen so that these patients were considered to have, in the unmet medical need situation. So, what does that entail? That means the patient should have been exposed to a proteasome inhibitor, to an immunomodulatory molecule, and to an anti-CD38 monoclonal antibody and should have received at least three or more prior lines of therapy and should be actually progressing on their last line of therapy. So with that requirement, if you look at it, the median number of prior therapy on the patients who participated was actually six. So patients were heavily pretreated. They had exhausted all available treatment options. So, they can participate in this clinical trial. And if not, there have been real-world evidence, such as LocoMMotion, which had reported what is the outcome for such a patient if they were treated outside of this clinical trial, if they were treated with the then available regimen. Their median progression free survival would have been only 3 months, and most patients would have lost their life within a year. So, this was truly an unmet medical need with patients in a very difficult clinical situation. Let's put it that way. So, those were the patients who participated in this particular trial. Dr. Davide Soldato: Thank you very much. And as we mentioned before, the results that were obtained in this clinical trial were really very interesting. And now, in this issue of the Journal of Clinical Oncology, you are reporting data with a longer follow up. So we are actually at more than 5 years of follow up for the patients included in this trial. So, I just wanted a little bit of insight into why you decided to report these long-term outcomes and what type of information do you think you could provide with this study to the medical community? Dr. Sundar Jagannath: This is very important because this was a clinical trial that was done in patients who were, as I said, in unmet medical need. Most of the patients had prior stem cell transplantation, had gone through a proteasome inhibitor. Many of them have had both Velcade and carfilzomib treatment. Most of them had been exposed to lenalidomide and pomalidomide. And as required, all of the patients had to have had prior exposure to anti-CD38 monoclonal antibody or daratumumab. So, the patients were heavily pretreated. Typically, TIL CAR T-cells came into the field at this particular moment, until then, we were developing small molecules, and they usually would have a PFS of 3 months and median life expectancy of a year, the overall response rate of 30%, and that is how, if you look back, that is how carfilzomib was approved, that is how pomalidomide was approved. So, the drugs which were approved, including daratumumab, you know, the response rate was in the same ballpark. So you would see that most agents, single agents, would have had a response rate in the neighborhood of 30%, the progression-free survival would have been between 3 to 5 months or 6 months at the most, and the life expectancy was short. And here comes a drug, and when I was following the patients at Mount Sinai, I found that there were a subset of patients, they got one-time treatment and they were in complete remission, no trace of cancer with annual evaluation with PET CT and bone marrow evaluation for MRD. So, I said this is remarkable, and this needs to be reported. And I went to the Janssen and company, and they agreed to review the entire experience. This is remarkable that 32 of the 97 patients, or one third of the patients, were alive and progression-free. This is unheard of for any clinical trial until now, that the patient will be progression-free, one third of the patients on a clinical trial will be progression-free, in the late stage of their disease. So that is the most important impact. And that is why this 5-year follow-up results were presented. Dr. Davide Soldato: Thank you very much. That was very clear. And as you said, we are speaking about a population that was heavily pretreated, that had exhausted all type of treatment options outside of a clinical trial. And as you said, one third of the patients was alive and progression-free after 5 years from being included and infused inside of the study. So, considering this population that, as we said, had received all treatment options, I was wondering if you observed any kind of differences in terms of disease characteristics when looking at these patients that had exceptional response, so, alive and progression-free at 5 years, and the patients that sadly had developed a progression after the infusion in the study. Dr. Sundar Jagannath: This is very important because we wanted to see who are the patients who are having this exceptional outcome. And we looked at all the 97 patients. If we look at all the patients, we saw that there were initially, out of the 97, 17 patients died earlier in the disease course due to treatment related complications, etc. But there were about 46 patients who had progression of disease and 32 patients, or one third, were alive without progression of disease. Then we looked at the 46 patients who had progression of disease. Of them, we found that 30 had disease progression and its complication, and there were actually 13 patients who were still alive even after progression of disease. So we decided to compare these 46 patients who had progression of disease versus 32 patients who had no progression of disease to see what is the difference. To our surprise, the age was similar, male, female distribution was similar. High-risk cytogenetics, which we would have thought, you know, that is why we say high-risk disease, the term, high-risk cytogenetics was equally distributed. That was really a surprise. Number of lines of prior therapy, number of exposure to drugs, all of that was the same. So that was also interesting. But a theme did emerge. Patients, in general, tend to have lower burden of disease who had the exceptional outcome. But there is one which we considered as bad, the extramedullary disease. Multiple myeloma being a blood cancer, it is usually in the bone marrow. When it starts growing outside of the bone marrow, the extramedullary disease, usually it portends poor prognosis. But we were surprised that actually there were an equal number of extramedullary disease patients even in the long-term survivor as those who had progressed of disease. So the most important takeaway was patients who had lower burden of disease, they had less number of myeloma cells in their bone marrow, percentage wise, and the soluble BCMA level was lower. Soluble BCMA is an indirect measure of the amount of plasma cells in the patient's body. It is like a tumor burden. So they were low. So, this was an important finding because it has future ramification, as you can understand. If this treatment is made available earlier in the disease course of the patients, where we are able to control the disease better, then more patients are likely to have such wonderful outcomes as one third of the patient experience in the late stage of the disease. Dr. Davide Soldato: So, you already mentioned soluble BCMA as a marker of potentially better prognosis as being correlated to a lower volume of disease. I was wondering if you could give us some more information about the biomarkers that you evaluated in the study. For example, you evaluated a little bit the CAR T expansion kinetics and also some others that I think could be interesting and could point to some population that experienced such important benefit. Dr. Sundar Jagannath: That is a very important point because CAR T-cell, it is a live cell and its efficacy depends upon how well the CAR T-cell is going to function. And then, you know, the patient undergoes apheresis. This is a patient's own lymphocyte. So first and foremost is who would generate good CAR T-cell. Those who have plenty of lymphocytes at the time they are coming for apheresis. This is likely to happen earlier in the course of the disease than in patients who have gone through numerous lines of therapy and exhausted. So, in this particular trial, of course this was in late stage of the disease, and so we were able to show patients who had lower number of T cell in circulation, and the way to measure is if they had more neutrophils and less lymphocytes. So that is what is called as a higher T cell over neutrophil, they did better. If they have more neutrophil than T cells, then they did not do well. So, procurement. The second one is also whether the T cells are more naive, you know, not exhausted T cells. So more naive T cells, if you are able to procure from the patient, they did very well. Now, after the CAR T-cell manufacture, then the expansion, when you put it back into the patient, if the T cells expand very well, so that the effector, that is the CAR T-cells to the tumor ratio is good, so there are more effector cells, the CAR T was able to expand and the amount of tumor was less, then the efficacy was very, very good. As I said, the patients in this group, those who had a lower burden of disease, they did better, and that is because of the CAR T-cell expansion, so the effector to the target ratio was favorable. So that is another important. And then there are also the type of CAR T-cells, having CD4 T cells with central memory phenotype at the peak expansion also makes a difference. So all of that matters. But this is important because the efficacy of the CAR T-cell, it is persistent, long persistent and keeping the cancer down. Its ability to get rid of the cancer completely at the first go around because usually we are not able to detect the CAR T-cells beyond 6 months in the majority of patients and very rarely after a year or two. So it is very uncommon to find the CAR T-cells in circulation or even in the regular bone marrow evaluation. So, efficacy, the expansion, having naive T cells, having good effector to target ratio and more central memory kind of T cell, because if it is all effector T cell, they will get quickly utilized and get exhausted, whereas the central memory cells can expand more and give more effective CAR T-cells. Dr. Davide Soldato: Thank you very much. I was wondering if you could guide us a little bit into what is your opinion regarding the positioning of CAR T-cells given all of these logistics that is necessary compared, for example, with bispecific antibodies against BCMA, which have the same target, but they do not have all of these logistics before being administered to the patient. Dr. Sundar Jagannath: That is a very important question, how to sequence these treatments now that we have two BCMA-directed CAR T-cells available. We have three BCMA-directed bispecific and one GPRC5D-directed bispecific antibodies are available. And so the question comes in for at least the currently approved CAR T-cell therapy, there is an obligatory time. You have to go through apheresis and you have to ship to the company, and there is a manufacturing time, roughly about 2 months before they can receive it. During that time, you want to make sure the patient's disease is under control. So that is a given. There are several ways to look at it when we evaluate the patient and talk to the patient. One good thing is now the two CAR T-cells which are approved, one is cilta-cel we talked about, and the other one is ide-cel. Ide-cel is approved in earlier line of therapy, two or more prior lines of therapy, and cilta-cel is approved in patients who have failed one line of therapy and who are lenalidomide refractory. So, the treatment of CAR T-cell is available earlier. And as I said, when you administer CAR T-cell earlier, you are able to keep the disease burden down, and it is a one and done deal. There is a better quality of life for the patient, and you are able to produce long, durable remission and potentially a cure. Now coming to the bispecific, they are currently available in later lines of therapy. So if you look at it from a patient's perspective, you can use the CAR T-cell earlier and then go through the bispecific therapy. But if the patient comes with relapsed refractory myeloma and has not used the CAR T-cell therapy and has not used the bispecific therapy, then the physicians have to decide which one they want to use. If somebody's disease is rapidly progressing and they need immediate tumor reduction and they have already exhausted all available therapy, then going through BCMA bispecific therapy is quite appropriate. And secondly, CAR T-cell therapy is generally given to somewhat physically more fit patients, whereas bispecific therapy, because you are giving antibody at step-wise dosing in this patient, and you have the ability to stop at any particular dose and then come back and redose, whereas CAR T is, you just give it to them one time, you have a lot more control. So intermediate frail or even frail patients can go through bispecific therapy, whereas it would not be in the best interest of the patient to go through a CAR T-cell therapy when they are frail. So that is another important point. But from the information available, when the patient goes on a BCMA bispecific therapy and they start progressing on treatment, usually it is their T cells are exhausted or the BCMA is no longer expressed on the tumor cells. So coming with CAR T-cell later on is usually not effective, whereas giving CAR T-cell earlier, if the patient relapses later, they have good T-cell function and most of the time the BCMA is still expressed. So you are able to give the BCMA to the maximum benefit by using the CAR T first and BCMA later. So if somebody asked me how to sequence this, just off the bat, you will say CAR T first, BCMA bispecific second. But as I said, there are unique situations. Then there is another potential that is happening. You can change the target. You can use a BCMA against GPRC5D to reduce the tumor, and then go ahead and consolidate it with a CAR T-cell therapy. That is also possible. You are changing the target from GPRC5D to BCMA, the tumor is already down, so the patient is likely to benefit. So these are all newer treatment options which have become available to the physician. So they will have to look at individual patients and decide what is the best course of action for that patient. Dr. Davide Soldato: So, I just wanted to close a little bit with your opinion about how these results translate into clinical practice. So considering this outstanding 5-year data that we have seen, one third of the patients who are alive and progression-free after a single infusion of cilta-cel, do you think that we could start to think about functional cure even in patients who have a diagnosis of relapsed refractory multiple myeloma? Dr. Sundar Jagannath: My feeling is this is important because in this particular study which is published, 12 patients who were followed at Mount Sinai out of the 32 patients who are alive and progression-free, 12 were followed at Mount Sinai. And they were evaluated every year with bone marrow MRD testing by clonoSEQ in 11 of the 12 patients, and one was by multiparametric flow cytometry. So most of them were 10 to the minus 6, not even one in a million cancer cells, and all of them had functional imaging, which is called PET CT every year. So these were patients who had no evidence of disease that we could detect with the technology available today, serologically, in the bone marrow, or anywhere else in the body with a PET CT. They were found to be disease free after a single infusion of cilta-cel. So, that would be almost to the definition of a cure because if you look at cure as a definition for any cancer, cure is defined as a state of complete remission with no trace of cancer that persists over a period of 5 years or longer without maintenance. And that will be applicable for breast cancer, lymphoma, leukemia. So it is a general statement. And if we use that in myeloma too, then I could say that these 12 patients from my center, we proved that they are cured of their myeloma. They are not functionally cured. You've got to remember, there is only cure. That was the definition across all diseases. So there is nothing like a functional cure. They are cured of myeloma. So is myeloma curable? This is the first time we are looking at that. We do know, every physician treating myeloma that there are patients out there, 10 year and beyond, without evidence of disease. This has been published by University of Arkansas, Bart Barlogie's group, who has been saying that myeloma is a curable disease for a long time. And many others have shown long-term follow up. But this one in a late stage disease, we were able to show that they were one treatment with no maintenance. All other studies have been in newly diagnosed myeloma patients. Nobody has shown in late relapse patients on a clinical trial a third of the patient will be progression-free. And 12 of them who were studied were actually disease free. So they were cured of the disease. So if we accept that, then the next question is, first step towards cure is achieving complete remission. They should have no monoclonal protein by any technology you want to use, no measurable residual disease using next gen sequencing or clonoSEQ, and functional imaging whole body PET CT or whole body MRI. So that is important, definition of the complete remission. And then it has to be sustained. That is something the IMWG and IMS, International Myeloma Society, they will have to come together for a consensus. How many years should they be followed and should be in this kind of status with no trace of cancer? Is it, 3 years are enough? 4 years enough? 5 years is enough? For me, I said in this paper, 5 years is a good definition for achieving a potential cure. Then you use the term 'functionally cured'. I have a problem with functionally cured and operationally cured or whatever. Functionally cured was originally put out by Paiva from Spain. There were 8% of newly diagnosed myeloma patients who have, after they go get treated, they will have an MGUS like phenomenon, a small amount of paraprotein detectable, and they are only 8%. And he said that these patients could be off treatment and the disease does not progress. But the problem is when you are giving treatment like maintenance therapy continuously until progression, you do not know exactly who is in the MGUS situation. So you have to have done sophisticated flow cytometry like Paiva did, and it is not quite clinically applicable. So functionally cured applies only for 8% of the people, so it should go out of the vocabulary. Then you can say 'operationally cured'. These are the patients traditionally Bart Barlogie and others showed that they have a large number of patients who have been followed for 10 years with no recurrence of disease, not on treatment. But in those days, they did not have MRD PET CT and all of them done systematically. So that is why they had to come up with a situation where they said they were operationally cured. So yes, myeloma patients have been cured since auto transplant was introduced. I completely agree. It is not new to the CAR T-cell therapy. But the beauty of the CAR T-cell therapy was it was in relapsed refractory myeloma, unmet medical need, number one. Number two, they were studied systematically. It was a clinical trial adjudicated by FDA and EMA for drug approval, cilta-cel was approved. So these patients were carefully followed, and it was a multi-center study. And in that group of patients, we were able to show patients- So, I think this would indicate cure is a reality in myeloma, and as these kind of treatments, immunologic treatment, either it is a CAR T-cell therapy or BCMA bispecific or whatever, there is a chance more patients are likely to be cured, and these treatments have to move forward and so that we are looking towards a cure. That is the beauty of it, and I just thank you for asking and also throwing in this so-called functionally cured, which people like to use casually, and I say it is time to talk more cure and not stuck with functionally cured because that does not allow the field to progress. Dr. Davide Soldato: Thank you very much. That was very interesting. Dr. Sundar Jagannath: And provocative. Dr. Davide Soldato: A little bit, but I think that we needed to close the podcast with this kind of reflection coming from someone who is an expert in the field, as you are. So, I really wanted to thank you for joining us today and for sharing more on your article, which is titled, "Long-Term Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma." If you enjoy our show, please leave us a rating and a review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. Dr. Sundar Jagannath: Thank you. 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.      

Julian Adams tried but didn't succeed at retirement after a productive career as a medical chemist with several U.S. Food and Drug Association approvals of cancer-related treatments, including cell therapy for bone marrow transplantation. Soon after, his participation in a Stand Up To Cancer advisory group led to his appointment as the nonprofit's president and CEO. The research organization raises money to advance the diagnosis of numerous cancers. Given rapid technological advancements, our podcast hosts were eager to invite Julian on the show to share how Stand Up To Cancer uses artificial intelligence to aid in this pursuit. Read the episode transcript here. For more information on Stand Up To Cancer and how to donate to the organization, please visit this website. Guest bio Julian Adams, president and CEO of Stand Up To Cancer, is among the world's foremost oncology researchers. He was previously CEO of biopharmaceutical company Gamida Cell and president of R&D at Infinity Pharmaceuticals, where he oversaw development of small molecule drugs to treat cancer. He has also held roles at Millennium Pharmaceuticals, Boehringer Ingelheim, LeukoSite, and ProScript. Adams's recognitions include the 2012 Warren Alpert Foundation Prize for his role in the discovery and development of bortezomib, an anti-cancer drug; the 2012 C. Chester Stock Award Lectureship from Memorial Sloan Kettering Cancer Center; and the 2001 Ribbon of Hope Award for Velcade from the International Myeloma Foundation. He holds more than 40 patents and has authored more than 130 papers and book chapters. He received his bachelor's degree and an honorary doctor of science degree from McGill University and his Ph.D. from MIT in synthetic organic chemistry. Me, Myself, and AI is a collaborative podcast from MIT Sloan Management Review and Boston Consulting Group and is hosted by Sam Ransbotham and Shervin Khodabandeh. Our engineer is David Lishansky, and the executive producer is Allison Ryder. Stay in touch with us by joining our LinkedIn group, AI for Leaders at mitsmr.com/AIforLeaders or by following Me, Myself, and AI on LinkedIn. We encourage you to rate and review our show. Your comments may be used in Me, Myself, and AI materials.

Episode 184: Multiple Myeloma BasicsSub-Interns and future Drs. Di Tran and Jessica Avila explain the symptoms, work up and treatment of multiple myeloma. Written by Di Tran, MSIV, Ross University School of Medicine; Xiyuan Yang, MSIV, American University of the Caribbean. Comments by Jessica Avila, MSIV, American University of the Caribbean. Edits by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Di: Hi everyone, this is Di Tran, 4th year medical student from Ross university.  It's a pleasure to be back.  To be honest, this project is a part of teamwork of two medical students, myself and another 4th year, her name is XiYuan.  She came from the AUC. Unfortunately, due to personal matters she was unable to make it to the recording today which makes me feel really sad. Jessica: My name is Jessica Avila, MSIV, American University of the Caribbean.Di: The topic we will present today is Multiple Myeloma. Multiple myeloma is typically a rare disease and it's actually a type of blood cancer that affects plasma cells in the bone marrow.Jessica: Let's start with a case: A 66-year-old male comes to his family doctor for an annual health checkup. He is not in any acute distress but he reports that he has been feeling tired and weaker than usual for the last 3 months. He also noticed that he tends to bruise easily. He has a history of arthritis and chronic joint pain, but he thinks his back pain has gotten worse in the last couple of months. Upon checking his lab values, his family doctor found that he has a calcium level of 10.8 and a creatinine level of 1.2, which has increased from his baseline. Given all that information, what do you think his family doctor is suspecting? And what kind of tests she can order for further evaluation?Di: Those symptoms sound awfully familiar – are we talking about the CRAB? You know, the diagnostic criteria for Multiple Myeloma.Jessica: Exactly! Those are called “myeloma-defining events.” Do you remember what those are?Di: CRAB criteria comes in 4 flavors.  It's HYPERCALCEMIA with >1mg/dL, RENAL INSUFFICIENCY with serum creatinine >2mg/dL, ANEMIA with hemoglobin value 10% plasma cells, PLUS any one or more of the CRAB features, we can make the official diagnosis of multiple myeloma. Di:  Before we go deeper, let's back up a little bit and do a little background.  So, what do we know about the immunoglobulins, also known as antibodies? Back from years of studying from medical school, we know that the plasma cells are the ones that producing the antibodies that help fight infections.  There  are various kinds that come with various functions.  Each antibody is made up of 2 heavy chains and 2 light chains.  For heavy chains, we have A, D, E, G, M and for light chains we have Kappa and Lambda.Jessica: Usually, the 5 possible types of immunoglobulins for heavy chains would be written as IgG, IgA, IgD, IgE, and IgM.  And the most common type in the bloodstream is nonetheless the IgG. Di: What is multiple myeloma? In myeloma, all the abnormal plasma cells make the same type of antibody, the monoclonal antibody.  The cause of myeloma is unknown, but there are lots of studies and evidence that show a number of potential etiologies, including viral, genetic, and exposure to toxic chemicals, especially the Agent Orange, which is a chemical used as herbicide and defoliant. It was used as a chemical warfare by the U.S. military during the Vietnam War from 1961 to 1971.Jessica: We need to order some specific blood tests to see if there is elevated monoclonal proteins in the blood or urine. So, to begin with we'll need to take a very thorough history and physical exam. Next, we'll do labs, such as CBC, basic metabolic panel, calcium, serum beta-2 microglobulin, LDH, total protein, and some not so common tests: serum protein electrophoresis (SPEP), immunofixation of blood or urine (IFE), quantitative immunoglobulins (QIg), serum free light chain assay, and serum heavy/light chain ratio assay.If any of the results is abnormal, we should consider referring our patient to an oncologist.Di: Interesting! I read that Multiple Myeloma symptoms vary in different patients.  In fact, about 10-20% of patients with newly diagnosed myeloma do not have any symptoms at all.   Otherwise, classic symptomatic presentations are weakness, fatigue, increased bruising under the skin, reduced urine output, weakened bones that is likely prone to fractures, etc. And if multiple myeloma is highly suspected, a Bone Marrow biopsy should be done with testing for flow cytometry and fluorescent in situ hybridization (FISH). Actually, if any of the “Biomarkers of malignancy (SLIM)” is met we can also diagnose multiple myeloma even without the CRAB criteria. Jessica: The diagnosis is made if one or more of the following is found: >= 60% of clonal plasma cells on bone marrow biopsy, > 1 lytic bone lesion on MRI that is at least 5mm in size, or a biopsy confirmed plasmacytoma. Di: Imaging comes in at the final step especially if we able to find one or more sites of osteolytic bone destruction > 5mm on an MRI scan.Jessica: What if the bone marrow biopsy returns > 10% of monoclonal plasma cells, but our patient doesn't have either the CRAB or the Biomarker criteria? Di: That's actually a very good question, since Multiple Myeloma is part of a spectrum of plasma cell disorders. That's when smoldering myeloma comes into play. It is a precursor of active multiple myeloma. Smoldering myeloma is further categorized as high-risk or low-risk based on specific criteria.A less severe form is called Monoclonal Gammopathy of Undetermined Significance, or simply MGUS, with < 10% bone marrow involvement. Those are diagnoses we give once we rule out actual multiple myeloma, which are defined by the amount of M-protein in the serum.Jessica:  When to get started on treatment? Multiple Myeloma is on a spectrum of plasma cells proliferative disorders, starting from MGUS to Smoldering Myeloma, to Multiple Myeloma and to  Plasma Cell Leukemia.  Close supervision/active watching is enough for MGUS and low risk Smoldering Myeloma. But once it has progressed to high-risk smoldering myeloma or to active Multiple Myeloma, chemotherapy is usually required. Some situations may require emergent treatment to improve renal function, reduce hypercalcemia, and to prevent potential infections.Di: As of 2024, treatment of Multiple Myeloma comprises the Standard-of-Care approved by the FDA. In fact, the quadruple therapy is a combination of 4 different class of drugs that include a monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug, and a steroid. Jessica: They are Darzalex (daratumumab), Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone.  Other treatment plans for Multiple Myeloma include chemotherapy, immunotherapy, radiation therapy (for plasmacytomas) and stem cell transplants. The patient will also be on prophylaxis acyclovir and Bactrim while on chemotherapy. Sometimes anticoagulants are also considered because the chemo increases the risk of venous thromboembolic events.Di: Although the disease is incurable, but with the advancing of novel therapies and clinical trials patients with multiple myeloma are able to live longer.  Problem is the majority of patients diagnosed with Multiple Myeloma are older adults (>65), the risk of falling is adding to multiple complications of the disease itself, such as bone density loss, pain, neurological compromises, distress and weakness.  Palliative care may come in help at any point in time throughout the course of treatment but is most often needed at the very end of the course. Jessica, can you give us a conclusion for this episode?Jessica: Multiple Myeloma may not be the most common cancer, but we have to be aware of the symptoms and keep it in our differential diagnosis for patients with bone pain, easy bruising, persistent severe headaches, unexplained renal dysfunction, and remember the CRAB: HyperCalcemia, Renal impairment, Anemia and Bone lesions.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:International Myeloma Foundation. (n.d.). International Myeloma Working Group (IMWG) criteria for the diagnosis of multiple myeloma. https://www.myeloma.org/international-myeloma-working-group-imwg-criteria-diagnosis-multiple-myeloma Laubach, J. P. (2024, August 28). Patient education: Multiple myeloma symptoms, diagnosis, and staging (Beyond the Basics). UpToDate. https://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics.University of California San Francisco. (n.d.). About multiple myeloma. UCSF Helen Diller Family Comprehensive Cancer Center. https://cancer.ucsf.edu/research/multiple-myeloma/about Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.

As part of a CancerNetwork® Frontline Forum program, Joselle Cook, MBBS; Matthew James Pianko, MD; Luciano Costa, MD, PhD; and Timothy Schmidt, MD, reviewed key data updates and real-world practice findings in newly diagnosed multiple myeloma (NDMM), and how they may impact patient subgroups including those with transplant-ineligible NDMM. Cook, a hematologist specializing in the management of patients with multiple myeloma at the Mayo Clinic in Rochester, Minnesota; and Pianko, a hematologist in the Division of Hematology and Oncology at The University of Michigan-Ann Arbor, led one part of the discussion. They discussed efficacy results from studies including the phase 3 MAIA study (NCT02252172), which assessed daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone vs lenalidomide plus dexamethasone in previously untreated multiple myeloma. They also spoke about the selection of patients with transplant ineligible multiple myeloma for triplet vs doublet induction therapy regimens and potential disparities in care for patients of racial and ethnic minorities. “We need trials to accommodate patients who are working [and patients] who are unpartnered, [and] we need to do more to understand the biologic drivers [of multiple myeloma] in Black patients,” Cook said. “Even though we have this explosion of [new] therapies onto the scene, we still have so much to do to make access to these novel treatments accessible and more equitable for everyone.” Costa, a professor of Medicine and director of the Multiple Myeloma Program at The University of Alabama at Birmingham, and Schmidt, assistant professor in the Division of Hematology, Medical Oncology, and Palliative Care within the Division of Medicine at The University of Wisconsin, also discussed updates in the multiple myeloma space, which included a review of findings from the phase 2 GRIFFIN trial (NCT02874742). In this trial, investigators assessed daratumumab plus lenalidomide, bortezomib (Velcade), and dexamethasone as a treatment for patients with transplant-ineligible NDMM. Costa and Schmidt also spoke about approaching consolidation and maintenance therapy for patients with transplant-ineligible NDMM. “As we're trying to move treatments into earlier lines of therapy—particularly things like bispecifics and CAR T—improving access is [something] that we as a field and as a community need to address,” Schmidt said.  Don't forget to subscribe to the “Oncology On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

Today we are talking to Barry Greene, CEO of Sage Therapeutics. Barry has had an amazing career spanning over 30 years in the biotech industry. Prior to Sage Barry was President of Alnylam shepherding it with John through its evolution from basic science through commercial product launch. Prior to ALNY Barry was general manager of Oncology at Millennium where he was directly involved in the approval and launch of Velcade. He is currently a member of the board of the Pharmaceutical Research and Manufacturers of America. 

Dr. Dominic Brandy discusses Natural Insights into Cancer with Dr. Ben Weitz. [If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.]    Podcast Highlights 2:25  Dr. Brandy explained that his journey started in September 2017 when he and his wife were on a Viking cruise and he read the book, How Not To Die by Dr. Michael Greger.  How Not To Die has lots of scientific references and shows that eating a plant based diet is associated with lower rates of cancer and other chronic diseases, including diabetes, cardiovascular disease, and dementia. Gregor also discusses the Blue Zones where Dan Buettner looked at regions in the world where people lived the longest, including Loma Linda, California, where most people are Seven Day Adventists and they are vegetarian, don't drink alcohol, and exercise a lot. The average woman there lives 10 years longer and the average man lives 14 years longer than the average American.  Dr. Brandy started right then to eat a plant based diet. 6:25  When Dr. Brandy came home the last week of September he was doing a surgery case and he felt a pop in his right collarbone.  This pain then got worse and worse and on November 10th he went to pick up a container of water and his clavicle cracked in half.  He went to the Urgent Care center and got an x-ray. Then he got an MRI and his orthopedic surgeon told him that he either had multiple myeloma or a cancer metastasis. He had a biopsy and lab work, which confirmed IgA multiple myeloma free Kappa chain. Dr. Brandy's oncologist recommended a triple drug regimen of a common medication for myeloma, a corticosteroid and Velcade, a proteasome inhibitor. Dr. Brandy accepted with the first two medications but rejected Velcade, because its common side effects include peripheral neuropathy, which is bad for a surgeon.  Then Dr. Brandy researched every thing he could do from a diet, lifestyle, and nutritional supplement perspective and started employing them.  He started taking various herbs, employed exercise, stress reduction, sleep, intermittent fasting, detoxification, and every month his numbers kept getting better and by six months he was in a complete remission.     Dr. Dominic Brandy is a plastic surgeon and anti-aging expert, but after being diagnosed in 2017 with multiple myeloma, an incurable blood cancer, he plunged himself into cancer research. He is now coaching cancer patients.  In addition to conventional therapy, he has adopted a natural approach to fighting cancer that includes a whole food plant based diet, daily exercise, and targeted nutritional supplements.   And now he has written a book, Beat Back Cancer Naturally, and he wants to share his approach with patients looking to prevent or treat cancer.   His website is NaturalInsightsIntoCancer. Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.     Podcast Transcript Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates and to learn more, check out my website, drweitz.com. Thanks for joining me, and let's jump into the podcast.                                 Hello, Rational Wellness podcasters. I'm very excited today that we'll be speaking with Dr...

In this podcast episode, Beth Faiman, PhD, MSN, APRN-BC, AOCN, discusses clinical considerations for diagnosis and optimal treatment selection for initial management of patients with multiple myeloma. Topics in this podcast include:IMWG criteria for diagnosing smoldering and active myelomaRisk stratification of smoldering myeloma with 2/20/20 criteria and active myeloma with R-ISS stagingIndividualizing initial treatment for ASCT-ineligible myelomaSelecting optimal initial treatment for ASCT-eligible myelomaPresenter: Beth Faiman, PhD, MSN, APRN-BC, AOCNNurse PractitionerCleveland Clinic Taussig Cancer InstituteCleveland, OhioCE/AAPA credit available by visiting the online program: https://bit.ly/3ee9IvsLink to full program, including downloadable slidesets: https://bit.ly/3ee9Ivs

Nancy Simonian is president and CEO of Syros Pharmaceuticals. Her conversation with Nature Biotechnology covers going against the advice of her mentor to take a job at Biogen; the long, winding path to approval for the multiple myeloma drug Velcade; and assisting her father in the operating room as a girl. See acast.com/privacy for privacy and opt-out information.

In this podcast episode, Suzanne Lentzsch, MD, PhD, and  Saad Z. Usmani, MD, MBA, FACP, discuss how they select optimal treatment for relapsed/refractory (R/R) multiple myeloma (MM) and answer audience questions from a live webinar. Topics include:Selecting optimal triplet regimen after first relapseSequencing treatment options after multiple relapsesManaging patient expectations when selecting treatmentsEmerging treatment options for R/R MMPresenters:  Suzanne Lentzsch, MD, PhDDirector, Multiple Myeloma and Amyloidosis ProgramProfessor of MedicineDivision of Hematology/OncologyColumbia University Medical CenterNew York, New YorkSaad Z. Usmani, MD, MBA, FACPClinical Professor of MedicineDepartment of Hematologic Oncology & Blood DisordersDivision ChiefPlasma Cell Disorders DivisionLevine Cancer Institute/Atrium HealthCharlotte, North CarolinaSupported by educational grants from Amgen; Bristol-Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; and Oncopeptides.Link to full program, including an downloadable slidesets and an on-demand webcast:https://bit.ly/3gjr62p

Heather Wolff joined Decibel in February 2018 as the head of clinical development operations for Decibel Therapeutics. Heather is responsible for Decibel’s clinical operations, regulatory operations, medical writing and data management functions, providing leadership around the company’s development programs. She has a long track record in clinical development, with a focus on building and leading data management groups. Widely recognized as a leader in the space, she has been a key member of both large and small companies including Infinity Pharmaceuticals, Millennium Pharmaceuticals (Takeda), Accenture (ACE), Synta Pharmaceuticals and Genetics Institute (Wyeth). She played a role in successfully gaining FDA approval for Wyeth’s rhBMP-2 in the U.S. and E.U., and also facilitated the acquisition of sNDAs for Millennium’s Velcade product. Heather graduated from Skidmore College with a B.A. in English.

At last year's ASH meeting, there was excitement around a new antibody drug conjugate targeting a protein called BCMA from Glaxo Smith Klein. Results from their Phase I study showed that patients who had relapsed immunomodulators (like Revlimid), proteasome inhibitors (like Velcade) and even monoclonal antibodies (like daratumumab), responded when taking this drug alone (60% response rate). Learn more from Dr. Maria Chaudhry of Ohio State University about current studies using this new drug and when patients could consider it in the course of their treatment.  Thanks to our episode sponsor, Celgene. 

Deborah Dunsire was a general practitioner in South Africa when a motorcycle drove her into industry. And that side trip, ultimately routing her to Boston, is still going on. She built the North American Oncology unit at Novartis, launched Gleevec, ran Millennium after the millennium, realized the value in Velcade, took a foray into Forum, and recently announced her latest role, President and CEO of XTuit Pharmaceuticals.