Podcasts about Amyloidosis

Drs. Dasgupta and Sarswat review how ATTR cardiomyopathy remains under-recognized despite its prevalence in older patients with heart failure, emphasizing clinical red flags across cardiac and systemic manifestations. They outline a practical diagnostic pathway that prioritizes early identification using light-chain evaluation, bone scintigraphy, and genetic testing to distinguish transthyretin subtypes and initiate timely, disease-modifying therapy.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/JYN865. CME credit will be available until May 23, 2027.Electrophysiologic Insights Into Transthyretin Cardiac Amyloidosis: From Red Flags to Rhythm Control In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/JYN865. CME credit will be available until May 23, 2027.Electrophysiologic Insights Into Transthyretin Cardiac Amyloidosis: From Red Flags to Rhythm Control In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/JYN865. CME credit will be available until May 23, 2027.Electrophysiologic Insights Into Transthyretin Cardiac Amyloidosis: From Red Flags to Rhythm Control In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/JYN865. CME credit will be available until May 23, 2027.Electrophysiologic Insights Into Transthyretin Cardiac Amyloidosis: From Red Flags to Rhythm Control In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

Drs. Sarswat and Dasgupta discuss contemporary decision-making in treating transthyretin amyloidosis, comparing oral stabilizers with subcutaneous silencers and emphasizing earlier diagnosis, phenotype-driven therapy, and individual patient preferences. They highlight how neuropathy and autonomic dysfunction influence choice of mechanism, review practical considerations such as side-effect profiles, dosing logistics, and drug–drug interactions, and briefly touch on emerging approaches like amyloid-removing and gene-targeted therapies.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

Today's guest is Mark McIntosh, founder of Victory Productions, a Denver-based non profit focused on lessening the impact of homelessness, education inequities and America's growing health issues concerning organ donation and wellness.Mark lives with Amyloidosis, whose treatment spared his life but destroyed his kidneys. Thanks to a kidney transplant to save his life, he now advocates and raises awareness for living organ donation. He is also the chair of the 2026 Denver Transplant Games, being held in June. We talk about the importance of organ donation, kidney health disparities among people of color, his 10 year mission to bring Colorado back to the healthiest state in the country, the National Transplant Games being held in Denver this year, and so much more!!Resources:Mark's Website: https://seekvictory.comMark's LinkedIn: https://www.linkedin.com/in/markmcintosh/Mark's Facebook: https://www.facebook.com/macanddoog/Transplant Games of America: https://www.transplantgamesofamerica.orgNational Kidney Registry: https://www.kidneyregistry.com/Follow:Follow me: https://www.instagram.com/melissagrosboll/My website: https://melissagrosboll.comEmail me: drmelissagrosboll@gmail.com

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/VXA865. CME/AAPA credit will be available until May 15, 2027.Hidden in Plain Sight: Recognizing and Referring Patients With Transthyretin Cardiac Amyloidosis in Internal Medicine In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/ZCE865. CME/AAPA credit will be available until April 27, 2027.Transthyretin Cardiac Amyloidosis: Integrating New Paradigms Into Cardiology Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and The Mended Hearts, Inc.. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/ZCE865. CME/AAPA credit will be available until April 27, 2027.Transthyretin Cardiac Amyloidosis: Integrating New Paradigms Into Cardiology Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and The Mended Hearts, Inc.. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/ZCE865. CME/AAPA credit will be available until April 27, 2027.Transthyretin Cardiac Amyloidosis: Integrating New Paradigms Into Cardiology Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and The Mended Hearts, Inc.. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/ZCE865. CME/AAPA credit will be available until April 27, 2027.Transthyretin Cardiac Amyloidosis: Integrating New Paradigms Into Cardiology Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and The Mended Hearts, Inc.. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/ZCE865. CME/AAPA credit will be available until April 27, 2027.Transthyretin Cardiac Amyloidosis: Integrating New Paradigms Into Cardiology Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and The Mended Hearts, Inc.. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/ZCE865. CME/AAPA credit will be available until April 27, 2027.Transthyretin Cardiac Amyloidosis: Integrating New Paradigms Into Cardiology Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and The Mended Hearts, Inc.. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

Dr. Michel G. Khouri reviews a landmark study examining patients with AL amyloidosis who achieved a complete cardiac biomarker response, highlighting profound improvements in cardiac structure, function, and long-term survival that rival the general population. The discussion underscores the transformative impact of early diagnosis and modern plasma cell–directed therapies, while reminding clinicians that ongoing multidisciplinary cardiac care remains essential even after sustained cardiac remission.

Dr. Monty Pal speaks with internationally acclaimed hematologists Dr. Vincent Rajkumar and Dr. Saad Usmani about the AQUILA trial in high-risk smoldering multiple myeloma, as well as advances in CAR-T and other evolving treatment strategies in the myeloma space. TRANSCRIPT Dr. Monty Pal: Hello everyone and welcome to the ASCO Daily News Podcast. I'm your host, Monty Pal. I'm a medical oncologist, underline medical oncologist, a professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. You're going to understand why I underlined "medical oncologist" there. I'm actually on the line today with two amazing hematologists. Today, we're going to actually explore treatments for high-risk smoldering multiple myeloma following the FDA's approval last year of daratumumab for the first-ever treatment of this indication. Now, this is based on the AQUILA trial, and this represents a huge shift in our traditional watch-and-wait approach to active disease interception. We're going to consider whether this landmark trial published in The New England Journal translates to day-to-day practice. I think it does, and we'll certainly make an argument for that. And I'm so fortunate today to have two internationally acclaimed experts here in the conversation: Dr. Vincent Rajkumar, senior author on the manuscript, and Dr. Saad Usmani, also an expert in his own right in myeloma. Dr. Rajkumar is the lead investigator of the AQUILA study. He's a professor of medicine and consultant in the divisions of hematology and hematopathology at the Mayo Clinic in Rochester, Minnesota. He actually chairs the Myeloma, Amyloidosis, Dysproteinemia Program. He is also editor-in-chief of the Blood Cancer Journal. Dr. Usmani, he and I actually go way, way back. We actually did the AACR Molecular Biology in Clinical Oncology course, I want to say in 2006, so this is our 20-year anniversary, Saad. He's the chief of the myeloma service at the MSK Cancer Center and a professor of medicine at the Weill Cornell Medical College in New York.  Saad, Vincent, welcome. Dr. Saad Usmani: Thank you so much for having me, Monty. Dr. Vincent Rajkumar: Yeah, thanks, Monty. A pleasure to be here. Dr. Monty Pal: Thanks. And just a quick note for our listeners, all of our disclosures are available in the transcript of this episode. First off, Saad, did I get that right? Was it 2006 when we did that course together? Dr. Saad Usmani: Yeah, 20 years. We are coming up to our 20-year anniversary. It's remarkable to have seen our careers move the way they have, Monty. Dr. Monty Pal: Oh my gosh. And for all the fellows who are on the line, that AACR Molecular Biology and Clinical Oncology course, it's sometimes overlooked. Wonderful primer on translational science. Okay, now we're going to get to the heart of the matter here, the AQUILA trial. So this was a study, Vincent, that you led. I wonder if you'd walk us through the primary endpoints in the study. What are we looking at in the AQUILA trial specifically? Dr. Vincent Rajkumar: Thanks so much. Again, as you mentioned, smoldering multiple myeloma has just been a condition that we watch and wait. And the first thing that I want to clarify here is that the AQUILA trial is looking at only a subset of smoldering multiple myeloma. That is the high-risk smoldering multiple myeloma. It was defined the way high-risk smoldering myeloma was defined at the time the trial was designed. It randomized 390 patients. One arm got daratumumab single agent in an attempt to delay progression to active myeloma and possibly prolong survival. And the other arm was the traditional observation. The primary endpoint, therefore, was time to active multiple myeloma. Other endpoints included time to when patients needed to start therapy for active multiple myeloma, which can vary based on physician judgment, and overall survival. Of course, response rate, complete response rate, and others were also endpoints. Dr. Monty Pal: That's interesting. And you know, I wanted you to riff a little bit on this definition of high-risk smoldering myeloma. Can you tell our audience how that's sort of evolved over the years? Dr. Vincent Rajkumar: Yes. I mean, if you step back, monoclonal gammopathy of undetermined significance has only a 1% per year risk of progression. Smoldering multiple myeloma, all comers have a 10% per year risk of progression. And over the years, trials have been done in the whole population, and then more recently, we felt we should really focus on the people with high-risk smoldering, defined as a 50-50 risk of progression in 2 years. That's like a 25% per year risk of progression in the first 2 years, which is a very high risk for the patient and something that would justify prophylactic intervention. And that definition initially was based on just high levels of monoclonal protein like more than 3 grams, the IgA subtype of myeloma, the suppression of uninvolved immunoglobulins. Others have used bone marrow flow cytometry markers, cytogenetics. Those combinations of factors were available at the time the AQUILA trial was designed, and a select combination was used. Later on, we found that we could match almost all of that in a very simple risk stratification using just the percentage of bone marrow plasma cells, the level of the M-spike, and the free light chain ratio, all three of which are available to all patients with smoldering at the time of diagnosis. So you don't need any special testing. So more than 20% plasma cells, more than 20 for the light chain ratio, and more than 2 grams for the M-spike. If someone has any two of the three, that is high-risk smoldering multiple myeloma according to the IMWG, but that definition, of course, came in 2020 after the AQUILA trial completed accrual. Dr. Monty Pal: That's interesting because this sort of flips the traditional paradigm where biomarkers get more and more complex as time goes on. Am I right in saying this sort of simplifies things a little bit? It uses standard laboratory or clinical parameters to gauge this category? Dr. Vincent Rajkumar: Absolutely. People were using suppression of uninvolved immunoglobulins, and those levels are not standardized, often vary by race. Also, the other aspect was the abnormal plasma cells on flow cytometry. Again, labs define it differently. So this makes it much more simple. But the IMWG also did a separate exploratory cohort within that paper where we added cytogenetics and we added scoring systems to improve on this further. So it simplified it for regular clinical practice and for like trials. But if you have a patient in front of you, the IMWG paper also has more complex scoring systems where you can take more than 20; 21 is more than 20, so is 51. And so, you can use the actual numbers that a patient has, additional variables like cytogenetics, and get a more refined estimate of what is the true risk of progression. Dr. Monty Pal: That's really helpful. Now, you told us about the primary endpoints, you've helped us define high-risk smoldering myeloma. Can you give us a sense of the top-line results from AQUILA? Dr. Vincent Rajkumar: Yes, I think the most important one was the primary endpoint, time to multiple myeloma, was at 5 years, the progression-free survival was 63% in the daratumumab arm compared to 41% in the observation arm. So, you know, approximately 60% of patients in the observation arm had already progressed by 5 years. And that number was about 40% for the daratumumab arm. We also looked at time to starting myeloma therapy, which is clinically actually quite meaningful because, you know, myeloma therapy means patients get a quadruplet for induction, they get stem cell transplant, they get endless maintenance, they get ongoing therapy virtually for the entire duration. So, preventing the need for myeloma therapy is in and of itself, I think, a major endpoint. And that at 3 years, 40% of people in the observation arm required full myeloma therapy compared to only 20% in the daratumumab arm. So there's a significant reduction in the risk of developing active myeloma as well as the need for myeloma therapy by using a time-limited 3 years of daratumumab single agent. Dr. Monty Pal: Perfect summary of the results. And maybe, Saad, I'm going to bring you into the conversation now. How does this sort of influence your day-to-day practice for smoldering myeloma? Is this something that you've incorporated for that high-risk subset? Dr. Saad Usmani: Thank you, Monty, and I agree. I think that's a really nice summary from Vincent. This study is very important for several reasons. It's actually the third clinical trial that has demonstrated that patients who are in the high-risk smoldering myeloma category benefit from an early intervention that delays the progression to active myeloma or to end-organ damage. And so having a nuanced discussion with our patients in the clinic becomes very important. Having this discussion around as an option becomes very important. And like Vincent said, when we look at that high-risk smoldering myeloma patient population, someone who has 22, 23% plasma cells versus, you know, 45, 50, you know, it's going to be a different discussion each time. But I think it's a very important first step. And I think this sets up the stage for us to design clinical trials where we can ask other questions on what would be better than daratumumab alone in terms of delaying progression in these patients. The other thing that I do want to highlight, and Vincent touched upon this a little bit, that the treatment in this clinical trial was for a fixed duration of treatment. So it was not forever treatment. This is maybe something that Vincent, you can even comment on a little bit more because the question we get after having this discussion is, "Okay, what do we do with patients who are going to be progressing to active myeloma?" Whether we can utilize anti-CD38 therapies for those. So Vincent, I would love your take on this too. Dr. Vincent Rajkumar: Yeah, I think, you know, the main philosophical change for me was previously, the thing was 'don't treat', and now for high-risk smoldering multiple myeloma, the question is, is daratumumab the best treatment or can we do something better? And those trials are thankfully ongoing. One of them has already completed accrual, isatuximab-len-dex versus len-dex. And another one is ongoing in ECOG, almost close to finishing accrual. And in the future, we'll be trying to see if we can use early intervention to even cure and prevent progression altogether.  So we are in this phase where we have one approved regimen, one approved drug, and we are not sure whether we can improve on that. The question is, "is a myeloma-like therapy better than monotherapy" would be the next question, and then what would we do further beyond that? In this context, whenever we have patients like this, one of the questions that comes up, as Saad mentioned, is how does this affect newly diagnosed myeloma therapy if somebody has been treated for smoldering and things like that? How will they be considered for clinical trials? Would they be considered as relapse myeloma or still newly diagnosed myeloma? And those are important discussions for clinical trialists to keep in mind, but I think for clinical practice, your duty is to the patient in front of you. If they have high-risk smoldering myeloma and there's data that there's treatments that can delay progression significantly, delay the need for myeloma therapy significantly, that's the highest priority. We'll cross that bridge.   There are so few patients going on clinical trials right now that if such a patient were to later on progress and wants to enter in a newly diagnosed myeloma trial later, years later, we can figure that out later. I feel like the most important discussion is what to do for that patient today. I still prefer a clinical trial if one was available. If one was not available, I'd prefer early intervention, but have an informed discussion with the patient because some of them may wish to delay therapy still. Some of them may have very borderline numbers that you want to watch them closely. Some of them may be having other comorbidities that prevent need for therapy. Some of them maybe have had the smoldering for a long time and you already know it's stable. So a lot of factors go in, and I think it's not a one-size-fits-all. Dr. Monty Pal: This is a terrific discussion, and you know, it sort of segues into maybe a question around biology. And this is something I was going to get to a little bit later, but Saad, I'm glad you brought it up. I'll liken it to the only thing I know, which is kidney cancer. So, you know, in kidney cancer, we use checkpoint inhibitors as adjuvant therapy. And there's this question of whether or not it breeds some resistance in the localized setting to ultimately what the patient might potentially be exposed to in the metastatic setting. Tell me your thoughts on this, Vincent, then maybe Saad separately. If you treat a patient with daratumumab in this high-risk smoldering setting, could it theoretically sort of limit options in the refractory setting now that we have regimens like DRBD that are kind of being utilized, or daratumumab with teclistamab? Vincent, I'll throw that to you first. Dr. Vincent Rajkumar: This is a great question, and it's usually asked when we've done the lenalidomide trials actually. We try to put the question back. If that was your concern, how would you actually solve it? Is it really biology that's going to answer that? Or is it a randomized trial? So the experiment has been done three times now where early intervention has been given. And if there was some detriment because of that, that would be reflected in the overall survival. In all three trials, there's no such detriment seen. In the first lenalidomide-dex trial, there was an improvement in overall survival. In the AQUILA trial again, the confidence interval doesn't cross one, and patients had better long-term survival on AQUILA, but certainly not less. We've also examined PFS2 data, and that doesn't seem to be affected. So yes, there is a theoretical concern, and that concern cannot be allayed for new treatments which we have not even tried, like tec-dara, and whether that effect would be there or not. But so far, I don't see it. And I think the onus is on proof of that in order to prevent people from getting early therapy. Dr. Monty Pal: Yeah. Saad, your thoughts on that? And before you jump in, I'll mention, we're kind of taking the same approach in kidney cancer, we're trying to really do studies to see whether or not, you know, immunotherapy rechallenge in these contexts, you know, really lends any substantial benefit. So far, the results have been interesting. I don't think we have enough numbers as yet to capture the impact of adjuvant therapy as it translates to metastatic, but I see so many similarities between the scenarios that you're facing in myeloma and what we're facing in RCC. Saad, your thoughts? Dr. Saad Usmani: Thanks, Monty. I'll go back to something that Vincent alluded to a few minutes ago about the way that we risk-stratify patients within smoldering myeloma. Right now, we are relying more on a disease burden-based stratification looking at the percentage of plasma cells in the bone marrow, the monoclonal protein, as well as the involved light chain versus the uninvolved light chain ratio. However, there are efforts underway to actually incorporate genomics into that schema and try to refine that definition of high-risk smoldering. And there have been two papers that came out in the latter half of last year. In fact. Dr. Rajkumar and I are co-senior authors on one effort where we can identify genomic myeloma in patients in precursor conditions. One of the key things that came out of that effort was that within the high-risk smoldering myeloma category, about 90% of the patients are genomically myeloma. So this whole debate of whether we need to intervene for those patients, I think, you know, we have sufficient biologic evidence that yes, we need to intervene for those patients.  I think that the next real step, like Vincent stated, is how do we intervene in those patients? And those clinical trials kind of are ongoing. We will probably need to have more validation of those genomic models being incorporated, but that's what I see in the future. I wouldn't be concerned for the patients being seen today with that query about the disease biology evolving because if I'm seeing a patient today in March of the first quarter of 2026 and offering them monotherapy daratumumab in their high-risk smoldering situation for the next 3 years and then they progress to myeloma after another couple of years, we are talking about what would be the treatment options for them in 2031, 2032. So I think the field is moving so fast, we have a lot of novel therapies coming into that frontline setting rapidly, so our options at that time would be very different. So, you know, I just wanted to kind of set up the stage for saying, you know, our tools are getting better in delineating which patients will need that intervention. And then eventually, I think, you know, we'll have much better options for newly diagnosed myeloma patients at the time when they need it in the future. Dr. Monty Pal: Just absolutely brilliant, absolutely brilliant. I love that summary. I think that you're absolutely right in saying that, you know, you've got to think about what you're going to do for that patient sort of in the moment, what's going to optimize their outcome and agree that the landscape is evolving very rapidly.  I'd be remiss, Saad, if I didn't ask you about something that I've been following in terms of your career trajectory. You've developed quite a reputation for your leadership in trials looking at CAR T-cell therapies for myeloma. Can you give us a sense of where that stands in broad terms? Dr. Saad Usmani: Certainly, Monty. I think the CAR Ts have slowly made their way from late relapse to early relapse. And now we have clinical trials that have completed accrual in the frontline setting comparing them to standard-of-care treatment for both older myeloma patients or transplant-ineligible patients, as well as younger transplant-eligible patients where we're actually trying to replace transplants with BCMA-directed CAR T-cell therapies. The nuance there would be we want to equal or better the survival outcomes that we've accomplished without compromising on the safety side of things for patients. Those therapies are moving into earlier lines. And more excitingly, you know, that's just the first wave of CARs. The next wave of CAR technology is coming, and it's going to be in vivo CARs where we may not need lymphodepleting chemotherapy, we may not even need as stringent regulatory nuances that we do for cellular therapies today. So, you know, I think the field is moving rapidly, and it's going to be a very interesting landscape to see over the next 5 to 6 years. Dr. Monty Pal: Yeah, you know, it's so interesting. I know in the solid tumor space, we're trying to replicate the success that you've had with CAR T and bispecifics, and I do see some light at the end of the tunnel. I'm seeing some really promising agents being developed, but clearly, we have so much to learn from our colleagues in hematology. Well, I have to tell you, this has just been a phenomenal conversation. Vincent, congratulations on your leadership of the AQUILA trial. Clearly, a big paradigm shift in the field. Saad, thank you for offering your expert insights and really giving us also a glimpse at the future of myeloma. Really appreciate having you both on the podcast today. Dr. Vincent Rajkumar: Thank you, Monty. Dr. Saad Usmani: Thank you so much. Dr. Monty Pal: And thank you so much to our listeners for your time today. Finally, if you value the insights that you hear from 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. Monty Pal    @montypal   Dr. Vincent Rajkumar @VincentRK Dr. Saad Z. Usmani @szusmani   Follow ASCO on social media:           ASCO on X     ASCO on Bluesky          ASCO on Facebook           ASCO on LinkedIn           Disclosures:        Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview      Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical    Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis    Dr. Vincent Rajkumar: Honoraria: Research to Practice, Medscape Patents, Royalties, Other Intellectual Property: Authorship Royalties from Up To Date Dr. Saad Usmani: Consulting or Advisory Role: Janssen Oncology, GlaxoSmithKline, Abbvie, Bristol-Myers Squibb/Celgene, Regeneron, AstraZeneca, Sanofi Research Funding: Janssen Oncology, Bristol-Myers Squibb, K36 Therapeutics, Abbvie, Regeneron  

In this episode of the Heart podcast, Digital Media Editor, Professor James Rudd, is joined by Professor Marianna Fontana from Royal Free Hospital in London, UK. They discuss the current and future state of therapies for ATTR amyloidosis affecting the heart. If you enjoy the show, please leave us a supportive review wherever you get your podcasts. It helps us to reach more people - thanks!   Link to published paper: https://heart.bmj.com/content/112/3/129

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on Atrial Fibrillation/Flutter in Transthyretin Cardiac Amyloidosis: Prevalence, Incidence, Clinical Predictors, and Effect of Tafamidis.

In this episode of JACC This Week, Dr. Harlan M. Krumholz and Dr. Carolyn S.P. Lam discuss a dedicated issue of JACC focused on cardiac amyloidosis—one of the fastest-evolving areas in cardiovascular medicine. They explore new evidence highlighting significant delays in diagnosing ATTR cardiomyopathy, the early divergence of mortality benefit with timely treatment, and why time to diagnosis is no longer a neutral factor. The conversation also examines secondary analyses from major clinical trials, practical guidance for amyloidosis evaluation and management, and Dr. Krumholz's Editor's Page on "computable diagnosis" as a moral imperative. This episode places emerging science in clinical context, emphasizing urgency, equity, and how clinicians should be thinking differently about diagnosis, staging, and access to therapy in amyloid heart disease. Read Full issue here: https://www.jacc.org/toc/jacc/87/5 Keywords: cardiac amyloidosis, amyloid heart disease, ATTR cardiomyopathy, computable diagnosis

Interview with Stewart Loh, PhD

Host: Darryl S. Chutka, M.D.  Guest: Julie Rosenthal, M.D.  Cardiac amyloidosis is not a common condition, but it is important for primary care clinicians to recognize it in our patients. It's commonly underdiagnosed as the symptoms are often assumed to be due to other, more common cardiac problems. Early recognition is important since this can result in improved treatment options and better patient outcomes. So how do we recognize cardiac amyloidosis? What are the presenting symptoms and what's the best way to establish an accurate diagnosis? I'll be asking my guest these questions as we discuss cardiac amyloidosis. My guest for tis podcast is Dr. Julie Rosenthal, a cardiologist in the Department of Cardiovascular Medicine at the Arizona campus of the Mayo Clinic.   Mayo Clinic Talks: Heart Health | Mayo Clinic School of Continuous Professional Development  Connect with us! Mayo Clinic Talks Podcast Season 6 | Mayo Clinic School of Continuous Professional Development 

With Felix Lindberg, Karolinska Institutet & Södersjukhuset Hospital, Stockholm – Sweden and Marianna Fontana, National Amyloidosis Center, University College London, London – UK. In this episode, Felix Lindberg and Marianna Fontana discuss the evolving landscape in the treatment of cardiac amyloidosis. After exploring the pathophysiology of cardiac AL and ATTR amyloidosis and recent years' insights about the epidemiology of these conditions, they focus on the transformation that has occurred in the therapeutic options for cardiac ATTR amyloidosis. The conversation addresses the key mechanistic differences and trial data on stabilizers and silencers, how to approach patient selection for these therapies, as well as emerging therapies including anti-amyloid antibodies. The discussion also highlights the importance of early diagnosis and key red flags that should elicit suspicion of cardiac amyloidosis. Suggested reading: Vutisiran in patients with transthyretin amyloidosis with cardiomyopathy. Fontana M, et al. N Engl J Med. 2025. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. Maurer M, et al. N Engl J Med. 2018. Efficacy and safety of acoramidis in tranthyretin amyloid cardiomyopathy. Gillmore JD, et al. N Engl J Med. 2024. CRISPR-Cas9 gene editing with nexiguran ziclumeran for ATTR cardiomyopathy. Fontana M, et al. N Engl J Med. 2024. Conventional heart failure therapy in cardiac ATTR amyloidosis. Ioannou A, et al. Eur Heart J. 2023. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Gillmore JD, et al. Circulation. 2016. Current landscape of therapies for transthyretin amyloid cardiomyopathy. Griffin JM, et al. JACC Heart Fail. 2025. Transthyretin amyloid cardiomyopathy: from cause to novel treatments. Fontana M, et al. Eur Heart J. 2026. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Garcia-Pavia P, et al. Eur Heart J. 2021. This 2026 HFA Cardio Talk podcast series is supported by Bayer in the form of unrestricted financial support. The discussion has not been influenced in any way by its sponsor.

AI Detection of Cardiac Amyloidosis   Guest: Patricia Pellikka, M.D. Host: Malcolm Bell, M.D.   Dr. Patricia Pellikka dives into the AI model she helped build. Working with an AI echo company, Ultromics Ltd., her team built an AI echo model to detect cardiac amyloidosis. The model works from an apical 4 chamber videoclip and was approved by the FDA via the breakthrough pathway. They have validated it internationally in a population with 22% prevalence of cardiac amyloidosis and it had a sensitivity of 85%, specificity 93%, PPV 78%, NPV 96%, and AUC 0.93.  The performance of the model was consistent across cardiac amyloid types; among AL, wild type ATTR, and hereditary ATTR, the sensitivity was 84%, 85%, and 86%, respectively.  The performance of the model was also superior to previously validated scores which use clinical and echocardiographic variables for detecting cardiac amyloidosis. The results of the study were published online in the European Heart Journal in July.   Topics Discussed: You have built an AI echo model to detect cardiac amyloidosis.  How did you get into this? Tell us about the model that you built. How did you validate it? How does the model compare with other screening methods for detecting cardiac amyloidosis? What are the next steps for your research?   Connect with Mayo Clinic's Cardiovascular Continuing Medical Education online at https://cveducation.mayo.edu or on Twitter @MayoClinicCV and @MayoCVservices. LinkedIn: Mayo Clinic Cardiovascular Services Cardiovascular Education App: The Mayo Clinic Cardiovascular CME App is an innovative educational platform that features cardiology-focused continuing medical education wherever and whenever you need it. Use this app to access other free content and browse upcoming courses. Download it for free in Apple or Google stores today! No CME credit offered for this episode.   Podcast episode transcript found here.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RCF865. CME/AAPA credit will be available until December 8, 2026.Contemporary Insights on Diagnosing and Treating Transthyretin Cardiac Amyloidosis: How I Think, How I Treat In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RCF865. CME/AAPA credit will be available until December 8, 2026.Contemporary Insights on Diagnosing and Treating Transthyretin Cardiac Amyloidosis: How I Think, How I Treat In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RCF865. CME/AAPA credit will be available until December 8, 2026.Contemporary Insights on Diagnosing and Treating Transthyretin Cardiac Amyloidosis: How I Think, How I Treat In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RCF865. CME/AAPA credit will be available until December 8, 2026.Contemporary Insights on Diagnosing and Treating Transthyretin Cardiac Amyloidosis: How I Think, How I Treat In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RCF865. CME/AAPA credit will be available until December 8, 2026.Contemporary Insights on Diagnosing and Treating Transthyretin Cardiac Amyloidosis: How I Think, How I Treat In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

JCO Editorial Fellow Peter Li and author Dr. Jahanzaib Khwaja discuss the  ASH 2025 Simultaneous Publication article, "A New Validated Staging System for AL Amyloidosis With Stage lllC Defining Ultra-Poor Risk: AL International Staging System." TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Peter Li: Welcome to this episode of JCO Article Insights. I am Dr. Peter Li, JCO's Editorial Fellow, and today, I am joined by Dr. Jahanzaib Khwaja on a new validated staging system on AL amyloidosis with stage lllC defining ultra-poor risk, AL International Staging System. This is a simultaneous publication that will be presented at this year's ASH Conference.  At the time of this recording, our guest has disclosures that will be linked in the transcript.  So, Dr. Khwaja, let's start off first: What would you say is the significance of your study? Dr. Jahanzaib Khwaja: Thank you very much. This is an important study in that, in the current treatment era, we have really improved outcomes of patients with systemic AL amyloidosis. Traditionally, the staging systems that have been employed, which are the Mayo 2012 and the European modification 2016, have been founded in eras where there were historic treatment protocols. So the significance of this new staging system is looking at outcomes of patients in the modern treatment era. That is patients who are treated with daratumumab-based treatments in the first line. And this is kind of the largest study which is externally validating a new prognostic model in the current treatment era with modern outcomes. Dr. Peter Li: Can you tell our listeners what is different about your new staging system? Dr. Jahanzaib Khwaja: The traditional staging systems, the Mayo 2012 and the European modification of 2016, looked at outcomes of patients with systemic AL amyloidosis with historic treatment protocols. And we know that they looked at outcomes according to an NT-proBNP and troponin, and in the Mayo 2012, they looked at it with the addition of the dFLC, which is the difference in the involved and uninvolved free light chain. Over the years, we have seen that outcomes have improved, and over decades, actually, outcomes are much better when we compare them to the previous decade. If we look at current treatment approaches, those traditional staging systems inadequately determine the poorest prognostic risk. So they are unable to tell us those who are going to perform poorly. Our current new validated staging system looks at the traditional NT-proBNP and troponin but uses the addition of the longitudinal strain. This is an echocardiographic parameter, and it is used widely in treatment centers who treat amyloidosis. This really identifies those ultra-high risk patients, and these are the patients who will perform poorly in current treatment protocols. And why is that important? Well, we need a robust staging system in the current treatment era which can stratify patients who will do well but also stratify those patients who do not do well. Because that is important for counseling patients, for risk stratification, for treatment approaches, and in the future, for designing clinical trials. Dr. Peter Li: And that is referring to the longitudinal strain greater than  -9% and NT-proBNP greater than 8,500 and then the high-sensitivity troponins greater than 50, which will define the new staging system. Can you talk more about how you picked these cutoffs and also what that alludes to in terms of the outcomes that you have discovered in this age of daratumumab-based therapy? Dr. Jahanzaib Khwaja: Yeah, that is a really excellent question because we have aimed to build upon traditional staging systems. So clinicians have used these traditional models for many, many years, and they have robustly underpinned our stratification of patients and how we counsel patients. So we didn't want to change some of these well-established thresholds, but we wanted to test them in the current treatment era. So the NT-proBNP of 8,500 and the high-sensitivity troponin of 50 were the traditionally used thresholds. And they actually stand the test of time. But we found that longitudinal strain additionally and independently predicts outcome independent of these other biomarkers. It is independent actually as a continuous variable, so you can cut this at a number of different stratification points and find independence. But we wanted to determine and discriminate those with the poorest outcomes. So we validated a longitudinal strain threshold of greater than  -9% by deriving this from a dataset of patients with the traditionally highest risk. Those are with European stage lllB. And looked at the optimal threshold with time-dependent ROC analysis. So we did this in our derivation cohort and then validated this externally in our external validation cohort amongst a number of centers in Europe, in the US, and in the UK. And it is important to note because longitudinal strain is an echocardiographic parameter, and traditionally the limitations are considered to be inter-vendor and inter-operator variability and intra-operator variability, and there are challenges with reproducibility of some of these measurements. So that is often cited as a limitation. But we found, when we have externally validated this across different centers using different platforms, actually the threshold of -9% is independently predictive of poorer outcomes independent of the traditional NT-proBNP and troponin thresholds, and it is robustly predictive of poorest outcomes. We know that those with stage lllC have a median overall survival of 4 to 7 months in the modern treatment era. And if we sub-stratify these by patients treated with daratumumab, outcomes have improved, but still, even if we look at daratumumab-treated patients, one-year overall survival is still only around 50 percent. So these are a poor risk group in the modern treatment era. Dr. Peter Li: Which kind of makes sense in a way because this kind of predicts whether they have amyloid-related cardiomyopathy. So I think this all tracks with our listeners. But given the poor outcomes even with daratumumab-based therapies, do you think this new staging system would change practice, if at all? Dr. Jahanzaib Khwaja: Yeah, I think that is a really good point because I think it comes to the question of why we use a staging system. What are its applications? I think one of the key things we think about in the clinic is how do we counsel patients when we first talk to them about their diagnosis. So there is a lot of information, but predominantly people want to know, what is my outlook going to look like? And as I say, in the bortezomib treatment era, 2010 to 2020, we used to say you have stage lllB, you have very poor outcomes, median survival maybe around six months. We have shown here that actually those with lllB have much better outcomes definitely over 12 months, up to 24 months in those with daratumumab-based therapies. So we need to counsel them in a different way. We then also need to say, "Well, who are the ultra-high risk?" So we said those with the longitudinal strain of greater than -9% with the traditional NT-proBNP and troponin cutoffs. And those patients will have poor outcomes. We need to talk about palliation. We need to talk about alternate treatment approaches. And then importantly for the community is about treatment and clinical trial design. So again, traditionally the traditional high-risk group lllB used to be considered an exclusion for all major trials. So these were excluded in the ANDROMEDA study, which led to the approval of daratumumab-based therapy, and multiple other trials. And we show here that actually patients with lllB should not be excluded from these studies because they do have good outcomes. And I think we make the important point that those with lllC, who do have poor outcomes, they need a different treatment approach, and we need to think about stratifying these patients differently. So perhaps the next modality of treatment will be the anti-fibril antibodies or a mode of treatment which can clear antibodies or clear the amyloid fibrils from the organs and reduce the organ toxicity early on. We know that those with lllC have poor outcomes particularly within the first year, and organ dysfunction really predominates here. So a different treatment approach is required, and we need to design trials specifically for these patients which look beyond anti-plasma cell clone therapy but also look at clearing the amyloid fibrils and improving organ function as this is predominantly the cause of death in these patients. Dr. Peter Li: That's an excellent point right there.  Do you foresee any limitations to this new staging system, or can you comment on is there potentially a better way to refine this staging criteria in the future? Dr. Jahanzaib Khwaja: Yeah, I think that is a really excellent point to consider, that staging systems always need refining across treatment eras. So we have looked at the bortezomib era, and then we have validated this in the daratumumab-based era. We know that amongst different countries access to treatment varies. We know that there are a number of factors which determine your health-related outcomes. That's access to healthcare, speed of diagnosis, access to tertiary diagnostics, ability to biopsy, and then supportive care. And I think our staging system highlights the importance of organ dysfunction predominantly causing death early on. And I think that as treatments improve this should be refined. So the expectation I think is, as we have better anti-plasma cell directed therapies, and as we hopefully develop anti-fibril antibodies and anti-fibril clearance drugs, that we will need to revalidate new models to effectively prognosticate in this treatment era. And I also think that as we become a bit more sophisticated with our approaches, we know that this can be refined in the future looking at other prognostic factors with regards to healthcare outcomes. I would say one of the strengths, however, of this model is that it builds on the traditional model, and it's quite simple to use. You just have the NT-proBNP and the troponin, and then longitudinal strain, which is used quite frequently in amyloid centers, and an echocardiogram is used in essentially all patients for diagnosis. So I think it will certainly be quite practical. But certainly I think, as you say, as treatment approaches change over time, and as we have further options in the future, we will need to refine prognostication. Dr. Peter Li: For the listeners out there, let's say someone comes in our clinic and we diagnose them with stage lllC amyloidosis. Can you comment on what clinical trials are out there that potentially they can refer their patients to? You mentioned anti-fibril therapy, which I think would be the way of the future. Can you kind of comment what you know at this current stage and point listeners in the right direction? Dr. Jahanzaib Khwaja: This is the challenge in amyloidosis. We don't have specific trials that are looking at those with the highest risk. And at present, even the ISA International Guidelines talk about risk according to the old treatment approaches and discuss attenuating our current chemotherapy approaches. And I think that for clinicians out there who identify those at the highest risk, it is really important to have a multidisciplinary approach, to consider palliation and palliative services early, and really work with your fellow cardiologists and renal physicians and neurologists to enable the best supportive care you have in order to deliver this anti-plasma cell directed therapy. We know that actually you only need for most patients small amounts of doses of chemotherapy to get good clonal responses, and we have seen that even in the bortezomib era that actually they have good CR rates and more impressive CR rates with daratumumab. But because of the organ dysfunction, it can be really challenging to deliver these doses. And supportive care is going to be really important particularly for these challenging patients. The future will be designing clinical trials that are appropriate for these patients. At present, we currently don't have available options, but I think the more we gather this data, the more we work collaboratively as a community, we will be able to mobilize our resources and get the best outcomes for these patients.  Dr. Peter Li: First build the field of dreams and then hopefully more therapies will arrive in the future. Thank you so much, Dr. Khwaja, for speaking about the JCO article, "A New Validated Staging System for AL Amyloidosis With Stage lllC Defining Ultra-Poor Risk: AL International Staging System," and for all your valuable input today. Dr. Jahanzaib Khwaja: Thank you very much. Dr. Peter Li: Make sure to check out the presentation at this year's ASH Conference taking place from December 6 to December 9. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcast. 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.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, the landscape of the pharmaceutical and biotech industries is marked by groundbreaking scientific advancements, regulatory shifts, and strategic collaborations that promise to reshape patient care and drug development significantly.A controversy has emerged in the wake of proposed changes to U.S. vaccine regulations by Dr. Vinay Prasad, a senior FDA official. This proposal has sparked considerable opposition from 12 former FDA commissioners who argue that these regulatory overhauls could potentially undermine public trust in vaccines. Former leaders from both the CDC and FDA have expressed concerns over these proposed vaccine policy changes during an ACIP meeting, discussions that could influence future public health strategies and vaccine trust. At a time when vaccine confidence is crucial, maintaining the integrity of regulatory processes is vital to public health efforts.Leadership changes are also afoot within the FDA, as Dr. Tracy Beth Hoeg steps into the role of acting director for the Center for Drug Evaluation and Research. Her appointment signals a shift towards leaders with direct experience in public health crises. This comes amidst further internal restructuring at the FDA, including the transfer of Theresa Michele, long-standing director of the Office of Nonprescription Drugs, indicating dynamic changes within the agency.In the realm of oncology, Eli Lilly's progress with its Bruton's tyrosine kinase inhibitor, Jaypirca, is noteworthy. The drug's expanded label now includes earlier treatment stages for chronic lymphocytic leukemia and small lymphocytic lymphoma. This expansion underscores the therapeutic potential of non-covalent BTK inhibitors and may significantly improve patient outcomes by offering earlier intervention options.Geopolitical challenges are impacting the industry as WuXi AppTec, a major China-based biopharmaceutical contractor, faces scrutiny from the Pentagon amid concerns about its potential ties with the Chinese military. This development highlights the complex interplay between global security concerns and international biotech collaborations. The intersection of global security concerns continues to impact biopharmaceutical supply chains as WuXi AppTec faces increased scrutiny from U.S. authorities.On the manufacturing front, Quvara Medical's emergence as a new contract development and manufacturing organization following Buckland Group's acquisition of a Becton Dickinson facility in the UK reflects industry trends toward consolidating manufacturing capabilities to meet growing biopharmaceutical demand efficiently.AstraZeneca is enhancing its pipeline through a renewed partnership with Neurimmune for an amyloidosis asset. This collaboration, potentially worth up to $780 million, highlights AstraZeneca's strategic focus on rare diseases and underscores their commitment to expanding their therapeutic portfolio through successful alliances.Regulatory updates from the FDA propose reductions in user fees for early-stage clinical trials conducted domestically while considering additional fees for overseas developments. This initiative aims to incentivize research activities within the U.S., potentially accelerating drug discovery timelines and fostering domestic innovation.In surgical technology advancements, Medtronic's Hugo surgical robot has secured FDA clearance for procedures involving prostate, kidney, and bladder removal. This marks a significant advancement in robotic-assisted surgeries and could enhance patient outcomes across approximately 230,000 surgeries annually in the U.S.As we explore more about financial maneuvers within this sector, Royalty Pharma's $275 million financing deal for Denali Therapeutics' Hunter syndrome drug reflects confidence in Denali's pipeline pendinSupport the show

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UBF865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 28, 2026.Exploring New Paradigms in Transthyretin Cardiac Amyloidosis Care: Experts vs AI In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UBF865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 28, 2026.Exploring New Paradigms in Transthyretin Cardiac Amyloidosis Care: Experts vs AI In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UBF865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 28, 2026.Exploring New Paradigms in Transthyretin Cardiac Amyloidosis Care: Experts vs AI In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UBF865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 28, 2026.Exploring New Paradigms in Transthyretin Cardiac Amyloidosis Care: Experts vs AI In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Alnylam Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

Evolving Treatment Landscape in Transthyretin Cardiac Amyloidosis   Guest: Rosalyn Adigun, M.D., Pharm.D. Host: S. Allen Luis, M.B.B.S., Ph.D.   In this episode of Mayo Clinic's “Interviews With the Experts,” Dr. Allen Luis interviews Dr. Rosalyn Adigun on transthyretin cardiac amyloidosis. Listeners will come away with a detailed overview of the evolution of treatment options for patient diagnosed with transthyretin amyloid cardiomyopathy, highlighting historical perspectives, early registration studies, current treatment options, and an outlook on future directions in the management of transthyretin cardiac amyloidosis.   Topics Discussed: Overview of the historical perspectives on the diagnosis and management of transthyretin amyloidosis. Current treatment options available for transthyretin amyloid cardiomyopathy, and factors that should guide a clinician's decision regarding the choice of therapy. Treatment options in the coming years. Ongoing research initiatives in the management of cardiac amyloidosis.    Connect with Mayo Clinic's Cardiovascular Continuing Medical Education online at https://cveducation.mayo.edu or on Twitter @MayoClinicCV and @MayoCVservices. LinkedIn: Mayo Clinic Cardiovascular Services Cardiovascular Education App: The Mayo Clinic Cardiovascular CME App is an innovative educational platform that features cardiology-focused continuing medical education wherever and whenever you need it. Use this app to access other free content and browse upcoming courses. Download it for free in Apple or Google stores today! No CME credit offered for this episode.   Podcast episode transcript found here.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE information, and to apply for credit, please visit us at PeerView.com/FRU865. CME/NCPD/CPE credit will be available until October 26, 2026.Implementing Targeted Therapies in Transthyretin Cardiac Amyloidosis: From Diagnosis to Stabilization In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE information, and to apply for credit, please visit us at PeerView.com/FRU865. CME/NCPD/CPE credit will be available until October 26, 2026.Implementing Targeted Therapies in Transthyretin Cardiac Amyloidosis: From Diagnosis to Stabilization In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from BridgeBio Pharma, Inc.Disclosure information is available at the beginning of the video presentation.

Host: Susanna Price Guest: Stephanie Schwarting Want to watch the episode? Go to: https://esc365.escardio.org/event/2176 Want to watch the extended interview on Arrhythmias in Cardiac Amyloidosis? Go to: https://esc365.escardio.org/event/2176?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests:  Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada.  Stephanie Schwarting has declared to have potential conflicts of interest to report: advisory board for Alnylam, Bayer, Pfizer; principal investigator in trials sponsored by Alexion, Novo Nordisk and Intellia. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Arrhythmias in cardiac amyloidosis Taking the 'O' out of HOCM: managing LVOT obstruction Snapshots Host: Susanna Price Guests: Carlos Aguiar, Stephanie Schwarting, Ahmad Masri Want to watch that episode? Go to: https://esc365.escardio.org/event/2176 Want to watch that extended interview on Arrhythmias in Cardiac Amyloidosis? Go to: https://esc365.escardio.org/event/2176?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Ahmad Masri has declared to have potential conflicts of interest to report: research grants from Pfizer, Ionis, Attralus, Cytokinetics and Janssen. Consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, Avidity, Neurimmune, and Tenaya. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Stephanie Schwarting has declared to have potential conflicts of interest to report: advisory board for Alnylam, Bayer, Pfizer; principal investigator in trials sponsored by Alexion, Novo Nordisk and Intellia. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/AJT865. CME credit will be available until October 14, 2026.Targeted Therapy for Hereditary Transthyretin Amyloidosis Polyneuropathy (ATTRv-PN): You Don't Want to Miss It! In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca and Ionis Pharmaceuticals.Disclosure information is available at the beginning of the video presentation.

Contributor: Aaron Lessen, MD Educational Pearls: The cause of Alzheimer's disease is multifactorial, but the most widely suspected mechanism is the amyloid cascade hypothesis: Beta-amyloid proteins accumulate in the central nervous system, forming plaques that impair neuronal function. In recent years, advances have led to the development of targeted therapies with monoclonal antibodies. These drugs: Work by degrading amyloid plaques Slow the rate of cognitive decline and disease progression Have major side effects, most notably the development of amyloid-related imaging abnormalities (ARIA) ARIA may present as edema, effusion, or microhemorrhages, which are only detectable on MRI Symptoms can include headache, vertigo, or focal neurologic deficits that mimic stroke For patients presenting to the emergency department with stroke-like symptoms, it is important to consider whether they have a history of Alzheimer's disease and whether they are taking these medications. This guides decisions about imaging and treatment: The work-up may require MRI, which can delay thrombolytic or endovascular therapy in patients with true strokeConversely, treating a patient with ARIA using thrombolytics increases the risk of bleeding and other complications References Ebell MH, Barry HC, Baduni K, Grasso G. Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis. Ann Fam Med. 2024 Jan-Feb;22(1):50-62. doi: 10.1370/afm.3050. PMID: 38253509; PMCID: PMC11233076. Ma C, Hong F, Yang S. Amyloidosis in Alzheimer's Disease: Pathogeny, Etiology, and Related Therapeutic Directions. Molecules. 2022 Feb 11;27(4):1210. doi: 10.3390/molecules27041210. PMID: 35209007; PMCID: PMC8876037. Perneczky R, Dom G, Chan A, Falkai P, Bassetti C. Anti-amyloid antibody treatments for Alzheimer's disease. Eur J Neurol. 2024 Feb;31(2):e16049. doi: 10.1111/ene.16049. Epub 2023 Sep 11. PMID: 37697714; PMCID: PMC11235913. Summarized by Ashley Lyons, OMS3 | Edited by Ashley Lyons and Jorge Chalit, OMS4 Donate: https://emergencymedicalminute.org/donate/

Interview with Frederick L. Ruberg, MD, and Mathew S. Maurer, MD, authors of Transthyretin Cardiac Amyloidosis in Older Black and Hispanic Individuals With Heart Failure. Hosted by Sadiya Khan, MD. Related Content: Transthyretin Cardiac Amyloidosis in Older Black and Hispanic Individuals With Heart Failure