POPULARITY
In episode 86 of the Podcast for Social Research, live-recorded at BISR Central, BISR's Ajay Singh Chaudhary and Danya Glabau sat down with fellow faculty Nafis Hasan to celebrate the launch of his new book, Metastasis: The Rise of the Cancer-Industrial Complex and the Horizons of Care. Nafis kicks off the discussion with a briefing on the successful cultivation of cancer cures for mice, but not humans, fundamental failures at the clinical level, the rise of cancer as a household name, and the blockbuster drug moving for $500,000 a shot. The three then discuss the primacy placed, among researchers, on genetic mutations above environmental causes, the notion of “financial toxicity,” and what it means to critique medical research at a moment of widespread cuts to public health institutions. Key questions arise along the way: why—despite the allocation of so many resources—are we not winning the war on cancer? Why has an entire political economy developed around genetic mutations, at the expense of public health campaigns—a more proven mitigator of cancer-related deaths? Why is capitalism so embedded in efforts to defeat cancer, and is there any alternative? Note: The Novartis drug with a half-million dollar price tag mentioned at the top of the podcast is Kymriah, not Keytruda. The Podcast for Social Research is produced by Ryan Lentini. Learn more about upcoming courses on our website. Follow Brooklyn Institute for Social Research on Twitter / Facebook / Instagram / Bluesky
This week's episode of “The Top Line,” is the final part of a three-part series diving into the latest advancements in cell and gene therapy manufacturing. In this episode, Fierce Pharma's Fraiser Kansteiner is joined by Bruce Levine, Ph.D., who is the co-inventor of Kymriah and the Barbara and Edward Netter Professor in Cancer Gene Therapy at the University of Pennsylvania. He's also joined by executives from CGT technology provider ScaleReady and regenerative cell therapy developer CellProthera. They dive into novel production approaches discussed earlier in this series, with a special focus on CAR-T therapies. To learn more about the topics in this episode: CAR-T hype faces infrastructure reality check CAR-T boxed warnings: What comes next? See omnystudio.com/listener for privacy information.
Dr. Christian Capitini is an associate professor and the Jean R. Finley Professor of Pediatric Hematology and Oncology. He serves as co-leader of the Developmental Therapeutics Program at the University of Wisconsin Carbone Cancer Center and director of clinical innovation at the Forward BIO Institute. He has received many awards for his clinical and research contributions, including the Department of Pediatrics Gerard B. Odell Research Award, the Outstanding New Member Science Award from the Society for Pediatric Research (SPR), and the Janet Rowley Award from the Jonas Center Cellular Therapy Symposium at the University of Chicago. Nationally, Dr. Capitini is an active member of the Society for Immunotherapy of Cancer (SITC) and serves as at-large director. Additionally, he serves on the executive board for the Pediatric Real World chimeric antigen receptor (CAR) T Consortium. Dr. Capitini leads an NIH-supported laboratory focusing on development of cell-based immunotherapies, including natural killer (NK) cells and CAR T cells, for the treatment of pediatric solid tumors. The Capitini Lab also develops alternatively activated macrophages for complications of bone marrow transplant, including graft-versus-host-disease (GVHD) and acute radiation syndrome. Dr. Capitini was one of the site principal investigators (PI) for the first multicenter CD19 CAR T cell trial, which led to the FDA approval of tisagenlecleucel-T (Kymriah) for relapsed/refractory B cell leukemia. Currently, he is site PI for a Kymriah trial related to the upfront treatment of high-risk B cell leukemia and for a multicenter GD2 CAR T cell trial for neuroblastoma and osteosarcoma through the Pediatric NCI-Cancer Immunotherapy Trials Network (CITN). He is also a sponsor and PI for a University of Wisconsin clinical trial expanding gamma delta T cells in vivo using zoledronate after alpha beta T cell depleted stem cell transplant. --- What We Do at MIB Agents: PROGRAMS: End-of-Life MISSIONS Gamer Agents Agent Writers Prayer Agents Healing Hearts - Bereaved Parent and Sibling Support Ambassador Agents - Peer Support Warrior Mail Young Adult Survivorship Support Group EDUCATION for physicians, researchers and families: OsteoBites, weekly webinar & podcast with thought leaders and innovators in Osteosarcoma MIB Book: Osteosarcoma: From our Families to Yours RESEARCH: Annual MIB FACTOR Research Conference Funding multiple $100,000 and $50,000 grants annually for OS research MIB Testing & Research Directory The Osteosarcoma Project partner with Broad Institute of MIT and Harvard ... Kids are still dying with 40+ year old treatments. Help us MakeItBetter. https://www.mibagents.org Help support MIB Agents, Donate here https://give-usa.keela.co/embed/YAipuSaWxHPJP7RCJ SUBSCRIBE for all the Osteosarcoma Intel
Synopsis: Bill Hinshaw is the President and CEO of Axcella Therapeutics, a clinical-stage biotechnology company pioneering a new approach to treat complex diseases using endogenous metabolic modulator (EMM) compositions. Bill entered biotech a little over four years ago following a long life sciences career in pharma, working for companies such as Novartis and Schering Plough. He joins host Rahul Chaturverdi for a discussion about where Axcella is from a development perspective and the therapeutic areas they're pursuing, the company's work to treat long Covid, the challenges of developing drugs to treat nonalcoholic steatohepatitis (NASH), and Axcella's “combination by design” multi-targeted approach to tackle complex diseases. Read More on Axcella Announces Positive Interim Data from Phase 2b EMMPACT Study of AXA1125 in Nonalcoholic Steatohepatitis (NASH) https://bit.ly/3U0iEa6 Biography: Mr. Hinshaw joined Axcella as CEO in May 2018. He is the former Executive Vice President of U.S. Oncology at Novartis Pharmaceuticals Corporation, having served 15 years with the organization. Mr. Hinshaw led all aspects of this >$6B organization, heading up more than a dozen product launches, including Tasigna®, Gleevec®, and Kymriah®; the integration of the GSK oncology portfolio; innovative medical, commercial, and market access models; and a patient-centric focus on education and support programs. He also played a key role on the Global Oncology Executive Committee, including leading key strategic programs to maximize the portfolio and pipeline development. Mr. Hinshaw was formerly the Head of the Northern and Central Europe Region for Novartis Oncology where he was responsible for leading all functions across 33 countries. Prior to that role, Mr. Hinshaw was the head of Group Emerging Markets, which included all divisions of Novartis in 50 countries worldwide. Prior to his role as EVP, Mr. Hinshaw held a number of lead roles for Novartis, including Head of the Hematology Business Franchise, which achieved >20% overall growth each year under Mr. Hinshaw's leadership. He also was the Global Head of Infectious Disease and Transplantation and Immunology (IDTI) based out of Basel, Switzerland, with responsibility for all functions of the organization, including commercial, development, BD&L, and strategy for the Business Unit. Other Novartis positions held by Mr. Hinshaw included Global Head of Infectious Disease Marketing and IDTI Development and Business Development & Licensing; Business Franchise Head, Infectious Disease; and Head of Infectious Disease Marketing. Mr. Hinshaw started his career at Schering Plough, where over the course of 12 years, he held a series of roles of increasing responsibility in the sales and marketing functions in both primary care and specialty business units, including market research, new products and in-line brand management, and sales positions at the representative, district, regional, and national levels. He also led the U.S. Oncology Unit where he was responsible for sales, marketing and business development. Mr. Hinshaw holds a B.S. in Molecular Biology from the University of Wisconsin.
Dr. Bruce Levine, Ph.D. (https://www.med.upenn.edu/apps/faculty/index.php/g5455356/p3504) is the Barbara and Edward Netter Professor in Cancer Gene Therapy, and the Founding Director of the Clinical Cell and Vaccine Production Facility (CVPF) in the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania. Dr. Levine received a B.A. (Biology) from University of Pennsylvania and a Ph.D. in Immunology and Infectious Diseases from Johns Hopkins, and is responsible for a range of important therapeutic “Firsts” including First-in-human adoptive immunotherapy trials that included the first use of a lentiviral vector, the first infusions of gene edited cells, and the first use of lentivirally-modified cells to treat cancer. Dr. Levine is co-inventor of the first FDA approved gene therapy (Kymriah), chimeric antigen receptor T cells (CAR-T cells) for leukemia and lymphoma, licensed to Novartis. Dr. Levine is co-inventor on 30 issued U.S. patents and co-author of over 200 manuscripts and book chapters with a Google Scholar citation h-index of 99. He is a Co-Founder of Tmunity Therapeutics (https://www.tmunity.com/), and of Capstan Therapeutics, both spin outs of the University of Pennsylvania. Dr. Levine is a recipient of the William Osler Patient Oriented Research Award, the Wallace H. Coulter Award for Healthcare Innovation, the National Marrow Donor Program/Be The Match ONE Forum 2020 Dennis Confer Innovate Award, serves as Immediate Past-President of the International Society for Cell and Gene Therapy, and serves on the Board of Directors of the Alliance for Regenerative Medicine. He has written for Scientific American and Wired and has been interviewed by the NY Times, Wall Street Journal, Washington Post, NPR, Time Magazine, National Geographic, Bloomberg, Forbes, BBC, and other international media outlets. The Tribeca Film Festival is currently debuting a documentary, Of Medicine And Miracles, tracing the transformative work in personalized cancer therapy, of Dr. Levine and his team - https://tribecafilm.com/films/of-medicine-and-miracles-2022
FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)
Listen to a soundcast of the May 27, 2022 FDA approvals of Opdivo (nivolumab) and Yervoy (nivolumab and ipilimumab) for advanced or metastatic esophageal squamous cell carcinoma, and Kymriah (tisagenlecleucel) for relapsed or refractory follicular lymphoma."”
Bristol Myers Squibb is once again piling on the cash for Immatics, a German immunotherapy biotech. The Big Pharma has tripled down on the collaboration, which originally kicked off in 2019 and was added to in 2021. BMS is paying $60 million upfront and $700 million in biobucks down the line for at least two new programs. And there's more: Bristol expanded the 2019 collaboration, with another $20 million plus milestones and royalties. Also under discussion is Fierce Pharma's special report on the world's 20 top-selling drugs. COVID-19 vaccines by Pfizer and Moderna are listed among the top three. And COVID treatments from Regeneron/Roche and Gilead were also in the top 20. Lastly, we have bloopers. After just over a month of creating this podcast, we finally have some “behind-the-scenes" tape to share. To learn more about the topics in this episode: The top 20 drugs by worldwide sales in 2021 ASCO preview: How Gilead, Pfizer, AstraZeneca-Daiichi breast cancer data may—or may not—change treatment practice ASCO: Mirati cedes to Amgen's Lumakras on durability in tight KRAS battle SKYLARK sings: Sage, Biogen hatch positive phase 3 data in postpartum depression GSK strikes $3.3B Affinivax buyout to MAP out challenge to Pfizer's blockbuster pneumococcal vaccine Pfizer, already flush with cash, will reap $16B from selling shares in GSK consumer health spinoff Roche's Evrysdi ramps up SMA rivalry with Novartis and Biogen thanks to FDA nod in newborns Novartis' Kymriah bags FDA nod to face off against Gilead's Yescarta in follicular lymphoma UPDATE: Bristol Myers triples-down on Immatics, bringing deal to $4.2B total biobucks. Why not just buy it? The Top Line is produced by senior multimedia producer Teresa Carey with editor-in-chief Tracy Staton, managing editor Querida Anderson and senior editors Annalee Armstrong, Ben Adams, Conor Hale and Eric Sagonowsky. The sound engineer is Caleb Hodgson. The stories are by all our “Fierce” journalists. See omnystudio.com/listener for privacy information.
Ukoniq, a treatment just approved last year, has been withdrawn; We rundown a host of drug pipeline news in asthma, dermatology and oncology; and there's positive results for a novel postpartum depression treatment.
Despite the successes of therapies like Kymriah and Yescarta against blood cancers, solid tumours remain difficult to treat. Finding appropriate molecular targets such as cancer-specific receptors is an ongoing challenge, while the physical environment of a solid tumour also plays a role in suppressing immune responses within it. That said, immunotherapy/cell therapy, like chimeric antigen receptor (CAR) and T cell receptor (TCR) therapies, has shown amazing promise in treating cancer patients where traditional therapies have failed. https://pancancer-t.com/ (Pan Cancer T) is a spinout from https://www.erasmusmc.nl/en/cancer-institute/patient-care (Erasmus MC Cancer Institute) in Rotterdam, the Netherlands. They are developing dual-action TCR cell therapies, a next-generation treatment for solid cancer that targets both the tumour and the immunosuppressive environment that they present. In this episode of BioInnovation Spotlight, Katrien Reynders-Frederix talks about the novel approach to TCR therapy at Pan Cancer T, her personal journey from biology to business, and why she wants to make a difference for patients. Pan Cancer T was founded by Prof. Reno Debets and Dr Dora Hammerl, and is supported by Thuja Capital, Van Herk Ventures, and Swanbridge Capital.
For episode three of Ori Spotlight, Bruce Levine, PhD., Barbara and Edward Netter Professor in Cancer Gene Therapy at the University of Pennsylvania Perelman School of Medicine and current President of International Society for Cell and Gene Therapy (ISCT) joins our host Jason C. Foster. Professor Levine pioneered the very first FDA approved CAR-T therapy Kymriah®and is a driving force across the cell and gene therapy industry, holding numerous positions at some of the most progressive CGT institutions in the world. In this episode he shares his perspectives on the industry shift that is needed to enable widespread access to these life-saving treatments and the responsibility of all stakeholders to make it happen. Learn more about Ori Biotech: www.oribiotech.com | Learn more about Professor Bruce Levine |
Извојевана велика победа за пацијенте са карциномом крви у Аустралији, одобрено је да се локално производи потенцијално спасоносна терапија.
In a major win for blood cancer patients in Australia, approval's been granted for a potentially lifesaving therapy to be manufactured locally. A state-of-the-art facility in Melbourne is to join just a handful of sites globally permitted to produce the CAR-T cell therapy Kymriah. - Во голема победа за пациентите со карцином на крв во Австралија, беше одобренa потенцијално спасувачка терапија што ќе се произведува локално. Најсовремен објект во Мелбурн ќе се приклучи на мал број места во светот на кои им е дозволено да произведуваат CAR-T клеточна терапија Kymriah.
ออสเตรเลียได้อนุมัติการผลิตเซลล์บำบัดเพื่อรักษาผู้ป่วยโรคมะเร็งระบบเลือดที่เรียกว่า CAR-T (คาร์ที) ซึ่งอาจช่วยชีวิตผู้ป่วยได้ โดยศูนย์เซลล์บำบัดล้ำสมัยในนครนครเมลเบิร์น กำลังจะได้เป็นส่วนหนึ่งในเครือข่ายทั่วโลก ที่ได้รับอนุญาตในการผลิตชุดเซลล์บำบัด ภายใต้เครื่องหมายการค้า “คิมรายห์ (Kymriah)”
In a major win for blood cancer patients in Australia, approval's been granted for a potentially lifesaving therapy to be manufactured locally. A state-of-the-art facility in Melbourne is to join just a handful of sites globally permitted to produce the CAR-T cell therapy Kymriah.
Dr. Stephen Hunger is a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In today's ASCO eLearning Podcast, Dr. Hunger will discuss two patient cases related to CAR T-cell therapy. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org. Transcription: The purpose of this podcast is to educate and inform. This is not a substitute for medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hi, my name is Stephen Hunger. I'm a professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, and chief of the Division of Oncology and director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. My career has focused on clinical, translational, and basic research regarding childhood Acute Lymphoblastic Leukemia, or ALL. One of the most exciting recent advances in cancer medicine is the development of Chimeric Antigen Receptor-redirected, or CAR-T cell therapy for relapsed in refractory pediatric B cell ALL. Today, I will present two cases that have similarities, but also important differences that highlight key questions and uncertainties regarding when and how to use CAR T cells in pediatric ALL. Currently the only CAR T cell product FDA approved for treatment of children and young adults up to age 25 with relapsed refractory ALL is tisagenlecleucel, trade name Kymriah. Additional CAR T cell products are in the late stages of testing, and will likely become FDA approved soon. My discussion today will focus on tisagenlecleucel, which can persist for years following therapy. Indeed, the first child treated at CHOP for ALL with CAR T cells in 2012 still has detectable CAR T cells over eight years later. Our first patient is Sue, who is currently 15 years old and has B-ALL that relapsed for the second time. She was first diagnosed at age 7, at which time she had an 80,000 white blood cell count. She was treated with standard chemotherapy with an excellent response, but relapsed during maintenance therapy 22 months following her diagnosis. Because this relapse occurred on therapy, she was considered high risk, and allogeneic transplant was considered the therapy of choice. She entered a second remission and became MRD negative after two cycles of consolidation therapy. Her brother was HLA identical, and she underwent a matched sibling transplant in MRD negative second remission following a cyclophosphamide mind plus total body radiation preparative regimen. She engrafted rapidly, had no GBHD, and was weaned off immunosuppression by six months post-transplant. One year post-transplant, she presented with bone pain and was found to have a second bone marrow relapse of B-ALL. Her leukemia cells were CD19 positive. Our second patient is 15-year-old Damian, who was diagnosed with CD19 positive B cell ALL four months ago. His initial white blood cell count was 80,000, and the cytogenetic and molecular studies did not show any known high or low-risk features or targetable lesions. He was treated with standard chemotherapy, but did not enter remission with 50% blasts at the end of four weeks of induction therapy. He received one month of consolidation chemotherapy with a Children's Oncology Group augmented BFM regimen, but still had 35% blasts after that therapy. He then received a four-week course of the CD3/CD19 BiTE blinatumomab, but again had 30% blasts at the end of that therapy. The blasts remained strongly CD19 positive. His 17-year-old sister is fully HLA matched. Both of these patients have relapsed refractory ALL, and meet the FDA approved indication for tisagenlecleucel, which is patients up to 25 years of age with B cell precursor ALL that is refractory or in second or later relapse. Sue is in her second relapse, and thus qualifies. Refractory is not defined precisely in the indication, but I think all would classify Damian as having refractory ALL, given that he has failed to enter remission with three different regimens. The pivotal trial that led to the approval of tisagenlecleucel was called ELIANA, and the results were published in the New England Journal of Medicine in 2018, with my colleague Shannon Maude being the first author. Of note, that study prohibited patients who had received prior CD19-directed therapy, so Damian would not have been eligible to enroll. However, the FDA label does not mention this, and many patients have been treated with tisagenlecleucel following earlier blinatumomab therapy. Thus, Sue and Damian are good candidates for tisagenlecleucel. Both are also medically in good condition without active infection or end organ dysfunction. There are also important differences between Sue and Damien. Sue has relapsed post-transplant while Damien has an HLA-matched sibling, but has never undergone transplant because he has never entered remission. Transplant with high level marrow disease, as he has currently, 30% blasts, is generally viewed futile, and the best transplant outcomes occur when patients are MRD negative immediately pre-transplant. A key current question in therapy of relapsed refractory ALL is whether CAR T cells should be used as a definitive therapy with responders receiving no subsequent antileukemia treatment, or as a so-called bridge to transplant, a means to get patients to an MRD negative state so that they can then undergo transplant as definitive therapy. There is no current definitive answer to this question, and these two cases help to highlight the issues to consider. Both Sue and Damian undergo T cell apheresis with a good collection. Cells are sent to the manufacturer to make the CAR T cells, a process that takes about four weeks. They receive low-intensity maintenance therapy for two weeks with adequate disease control, and then no therapy is given for two weeks. Both have adequate manufacture of CAR T cells, and then receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by CAR T cell infusion. Both patients have mild signs of cytokine release syndrome not requiring intervention. At day 30 post-infusion, both Sue and Damian are in an MRD negative complete remission and have no detectable circulating B cells. What should happen next? While some feel that the long-term efficacy of CAR T cells have not yet been established, and that transplant should be used as a consolidative therapy in almost all cases, many others believe that a long-lasting CAR T cell product such as tisagenlecleucel can be used as definitive therapy in some cases. In the initial ELIANA publication, 81% of the 75 relapsed refractory ALL patients infused with tisagenlecleucel obtained in MRD negative complete remission within three months, usually after one month. And the 12-month event-free survival and overall survival rates were 50% and 76%. More mature survival data from ELIANA shows a two-year relapse-free survival rate of 61% among those achieving remission. Like Sue and Damian, the patients in this trial were heavily pretreated with a median of three prior regimens and 61% had previously undergone transplant. Knowing that many patients can survive long term with no further therapy post-CAR T cell infusion, there is limited enthusiasm for a second transplant among physicians, patients, or their parents if a good response is obtained and maintained. So for Sue, I would recommend close monitoring, but no additional therapy as long as she showed continued evidence of response for 6 to 12 months. I would repeat bone marrow MRD testing at 60 and 90 days and every three months thereafter, and measure peripheral blood B cell numbers monthly for at least six months. B cell depletion is a good surrogate for CAR T cell activity, as normal CD19 positive cells are also killed. If Sue remains MRD negative and has no circulating CD19 positive B cells for at least six months, then there is a good hope that no more therapy is needed. Damian is a more complicated case, as he has never undergone transplant and has an HLA-identical donor, and now has excellent disease control and is in good medical condition to undergo a transplant. There are short-term risks of transplant with a 100-day mortality risk of 5% to 10% for a teenager. And there are also long-term risks related to the transplant procedure and/or graft versus host disease. The long-term risks of tisagenlecleucel appear limited other than the persistent B cell depletion, but the longest followup is only eight years, and few patients have more than five years of followup. So we have no idea about the efficacy and potential risks 10 to 20 or more years post-infusion. Damian failed three induction attempts. If his leukemia comes back, one may never be able to get him back into a healthy MRD negative remission. So there is a good argument that his best chance for definitive therapy is with transplant. Given this, many would strongly recommend transplant as consolidative chemotherapy for Damian. However, it's also possible that Damian has now received curative therapy and will never relapse. Highlighting the uncertainty surrounding this question, our group at CHOP, which has treated over 300 patients with relapsed refractory ALL with CAR T cells, does not have a clear consensus on what to do for patients like Damian. It's our practice to summarize the potential advantages and disadvantages of transplant versus no further therapy, and help the patient and their family decide what is the best course for them. To summarize, tisagenlecleucel is an exciting therapy that provides new opportunities for children and young adults with relapsed and refractory ALL. However, the field of cellular immunotherapy is young, and there are many uncertainties, particularly surrounding the issue of definitive therapy versus bridge to transplant. Today, we lack the followup data needed to make definitive statements, and patients and families need to understand that and be full partners in these complicated decisions. Thank you very much for listening. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.
In today's episode, we hear from Dr. Raghuveer Ranganathan, a clinical instructor in the Division of Hematology and Oncology at the UNC School of Medicine at Chapel Hill. His clinical focus is lymphomas and leukemias, with a specific focus on using cellular immunotherapy to treat patients with hematologic malignancies. Dr. Ranganathan discusses how the treatment landscape has changed with the introduction of CAR-T therapies and other advances in cellular immunotherapy techniques. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carol, a reporter for the ASCO Daily News. Today I'm speaking with Dr. Raghuveer Ranganathan, a clinical instructor in the Division of Hematology and Oncology at the University of North Carolina's School of Medicine at Chapel Hill. His clinical focus is lymphomas and leukemias, with a specific emphasis in using cellular immunotherapy to treat patients with hematologic malignancies. His research on cellular immunotherapy techniques, such as optimized TCR and CAR T-cells, has been published in peer-reviewed journals, and his work has been recognized by the Lymphoma Research Foundation and the American Society of Hematology. Dr. Ranganathan reports no conflicts of interest relevant to this podcast, and full disclosures relating to all Daily News podcasts can be found on our episode pages. Dr. Ranganathan, welcome to the podcast. Dr. Raghuveer Ranganathan: Hi, Geraldine. Thank you for inviting me and having me on your podcast today. ASCO Daily News: Dr. Ranganathan, how has the treatment landscape changed with the introduction of CAR T- cell therapies for hematologic diseases? Dr. Raghuveer Ranganathan: The CAR-T therapies have really revolutionized our treatment options in general. Currently, the main pillar of front-line treatment for hematologic malignancies is chemotherapy, with radiation sometimes playing a supportive role, and surgery being a rare adjunct. Now immunotherapy, and specifically cellular immunotherapy, has formed an additional and critical option for these diseases, especially in the relapsed refractory setting. In particular, CAR T-cell therapy has provided hope in achieving long-term remissions, and maybe even a cure in patients, with these hematological cancers who are chemorefractory, or have exhausted all other treatment modalities due to the persistence of their disease. Interestingly, due to the success in multiple-relapse refractory disease, CAR T-cell therapy is being explored as an option earlier to patients with relapsed refractory disease. As stated, chemotherapy is still the front-line option for hemotological malignancies. As an example, for diffuse large B-cell lymphoma that is not a double- or triple-hit variant, the standard of care is still R-CHOP as front-line therapy. And if the patient relapses systemically, then the goal is to give salvage chemotherapy, with the hope of proceeding to an autologous stem cell transplant, if they're in CR and transplant-eligible. CAR-T is approved for a second relapsed disease and beyond in lymphomas. It's thought, though, that patients who have been exposed to high-dose chemotherapy or numerous salvage chemo regimens display less P-cell fitness overall, which subsequently reduces the cytotoxic efficacy of CAR T-cells derived from those patients' regular T-cells. As a result, there are ongoing clinical trials comparing the use of CD19 targeting CAR T-cell therapy with aggressive B-cell lymphoma in first relapsed, and comparing it prospectively against autologous hematopoietic stem cell transplants. ASCO Daily News: So what are some of the recent FDA drug approvals for CAR T-cell therapy that you are now using when treating lymphoma patients, and what you expect to see approved in 2020? Dr. Raghuveer Ranganathan: So there are two currently FDA-approved CAR-T products that are now available for commercial use. Both CAR-T products target a CD19 antigen present on B-cell derived hemotological malignancies. One of them is axicabtagene ciloleucel, otherwise known as Axi-Cel, or its trade name of YESCARTA. And it's FDA-approved for use in adult patients who have received two or more lines of therapy for relapsed refractory aggressive B-cell lymphomas, which includes diffuse large B-cell, including high-grade variants, primary mediastinal B-cell, and transform follicular lymphomas. The other CAR-T product is also CD19-targeting, named tisagenlecleucel, which we will call as Tisa-Cel, its trade name being KYMRIAH. And it has two indications as part of its approval. One is for adults with relapsed refractory diffuse large B-cell lymphoma, including high-grade variants and transport and follicular lymphomas. So in other words, the indication's very similar to Axi-Cel, except with the exclusion of primary mediastinal B-cell lymphoma. The second indication for Tisa-Cel is for use in children and young adults up to the age of 25 years with B-cell acute lymphoblastic leukemia, or B-cell ALL, that is either refractory to treatment or has relapsed twice or more. The main difference between the two CD19 CAR constructs molecularly is that Axi-Cel has a CD28 intracellular costimulatory domain, while Tisa-Cel uses a 4-1BB costimulatory domain. Axi-Cel had an initial overall response rate and a complete response rate of 82% and 58% respectively, with ongoing complete response rates of about 35% at six months in its ZUMA-1 phase 2 trial. Tisa-Cel displayed an initial overall and complete response of 53% and 40%, respectively, with ongoing Complete Response, or CR rate, at six months of 30% in its Juliet phase 2 trial in its patients. In both trials, those patients who reached and remained in CR at eight to 10 months displayed a high chance of remaining in complete remission long-term. Several patients in both trials demonstrated conversion of a partial response to a complete response as much as 15 to 18 months after Cartesian infusion, though most of these conversions happened within the first six months. It's difficult to compare the clinical trials for each of these CD19 CAR-T products with each other because each of the trials were conducted in critically different ways regarding patient selection, disease types, allowing bridging therapy or not, and different dosages of lymphodepletive chemotherapy. How these differences matter clinically is yet unknown and requires more research at this time. However, there were some interesting similarities and results between the two trials. Patients both below age 65 and above 65 did equally well. Germinal center and non-germinal center lymphomas both responded equally to both CD19 CAR-T products. Both trials include a small number of patients with CD19 negative lymphomas, and some of them responded to CAR-T therapy. Also interestingly, the early use of tocilizumab, which is an aisle 6 receptor-blocking antibody used in cases of Cytokine Release Syndrome, or CRS, did not negatively impact response outcomes, and neither did the early use of corticosteroids for CRS and/or neurotoxicity. Now, in addition to the Axi-Cel and Tisa-Cel, a third CD19-targeting CAR-T product, lisocabtagene maraleucel, or Liso-Cel cell for short, is supposedly nearing FDA approval for 2020 in relapsed refractory lymphoma. Its distinct feature, compared to the other two products, is that Liso-Cel is formulated as specified CD4, CD8 composition ratio administered at a flat dose. At the recent ASH meeting in December 2019 in Orlando, Liso-Cel showed promising response rates that were comparable to Axi-Cel and tisagenlecleucel in relatively short follow-up time. And the pure publication of the data from its clinical trials is still eagerly awaited. ASCO Daily News: Right. And what about the use of CAR-T therapy in mantle cell lymphoma? Dr. Raghuveer Ranganathan: So relapsed mantle cell lymphomas, especially with blastoid or pleomorphic morphologies, have a dismal prognosis with available salvage therapies. And this is where CAR-T can hopefully help. At the recent ASH meeting, the ZUMA-2 clinical trial with Axi-Cel in mantle cell lymphoma showed very promising response rates. An overall response rate of 93%, with 67% CR rate, was seen in 68 patients, with most of these patients having relapsed after autologous hematopoietic cell transplants. And the majority showing refractory disease to BTK inhibition, which is the standard therapy after a first relapse. The CAR-T therapy results appeared to be agnostic towards the morphology of patients' mantle cell lymphoma. Meaning those with the more aggressive blastoid or premorphic variant morphologies responded as well as those with the classical morphologies. Grade 3 or higher CRS neurotoxicity were seen in 15% and 31% of patients, respectively. And we're waiting for the official publication of these results as well to gauge its full efficacy and safety profile in this disease sub-type for lymphoma. ASCO Daily News: Let's focus on patients with multiple myeloma for a moment. How does CAR T-cell therapy differ for patients with multiple myeloma? Dr. Raghuveer Ranganathan: So multiple myeloma tumor cells rarely express CD19. So CD19 is not really regarded as a dependable target for myeloma. B-cell Maturation Antigen, or BCMA for short, is a trans-membrane protein which is expressed on multiple myeloma cells. There have been a handful of phase 1 trials looking at BCMA-targeting CAR T-cells in multiple myeloma. And the first phase I trial was out of the NCI published in 2015, looking at 12 patients who received anti-BCMA CAR at varying dose levels where they had one stringent CR and two very good partial responses, and one partial response, with response durations lasting between 16 and 30 weeks. But eventually all of the patients relapsed, unfortunately. A follow-up trial by the same group using a different anti-BCMA CAR, with a 4-1BB post-stimulatory domain, instead of the CD28 domain used in the first trial, was used in the multi-center phase I trial with 33 patients enrolled. Similar to their first trial, the new trial had varying dose levels of the anti-BCMA CAR cells as well, and had slightly higher doses given than seen in CD19 CAR trials. An overall response rate of 85% was seen, with 45% CR or stringent CR. Very good partial response and better were only seen in the higher dose levels of at least 150 million CAR-positive T-cells or higher. Four of these patients showed ongoing CR or stringent CR of 12-plus months at the time of study publication. In a subset analysis of patients whose myeloma tumor expression of BCMA was less than 50%, and comparing them to patients whose BCMA expression was greater than 50%, there was no difference in response. 16 out of 18 patients who were assessed for MRD negativity were negative at 10 to the minus 4 nucleated cells, and median progression-free survival was 11.8 months. Another phase 1 trial out of University of Pennsylvania, using a fully-humanized anti-BCMA CAR, was administered to 25 patients, either with or without lymphodepletive conditions prior to CAR-T infusion. In the cohort of 11 patients receiving both lymphodepletion and a higher CAR-T infusion dose, an overall response rate of 64% was seen. Since publication of these studies, unfortunately though, the majority of the study patients have all relapsed with disease. It is somewhat difficult to pinpoint the reason for this large amount of relapse, but it might have something to do with the nature of the BCMA antigen itself. BCMA is cleaved by an enzyme called gamma secretase and shed off of the surface of myeloma tumor cells normally. High levels of soluble BCMA circulating in the peripheral blood, incidentally, is associated with a poor clinical outcome in general. While the study showed efficacy in a myeloma tumor whose BCMA expression was less than 50%, there is very likely an expression level below which the CAR T-cells will not be effective in identifying and eliminating a tumor. And since BCMA can be cleaved off the myeloma cell surface, it's basically an escape route for the tumor cells to evade detection from the BCMA-targeting CAR. Interesting data shown at the recent ASH Conference out of the Fred Hutchinson Cancer Center showed the addition of an inhibitor of gamma secretase keeps the BCMA from being cleaved and shed off of the myeloma tumor cell surface, thereby increasing its expression levels and keeping it on the tumor cell surface. When the gamma secretase inhibitor is combined with anti-BCMA CAR-T cells in patients, it preliminarily showed promising long-standing results in a phase 1 trial with six patients. But further follow-up and additional clinical trials are necessary to validate these findings. Additionally, here at UNC Chapel Hill, we have a clinical trial open that uses CAR T-cells targeting CD138, which is another antigen also expressed on myeloma cells instead of BCMA. We're currently enrolling patients and hope to see an efficacy in myeloma, which would help advance the treatment paradigm from our studies as well. ASCO Daily News: Excellent. Well, Dr. Ranganathan, I think it's important to address the issue of toxicities. So how are the toxicities unique to CAR-T being addressed? And do you foresee a time when biomarkers will be used to predict toxicity in patients? Dr. Raghuveer Ranganathan: Sure. The two toxicities uniquely seen with CAR-T therapy are Cytokine Release Syndrome and Neurotoxicity, otherwise known as ICANS. The pathophysiology of these two toxicities is still somewhat unknown, and an area of concerted investigation currently. Cytokine Release Syndrome, or CRS, is a systemic inflammatory response produced by a superphysiologic elevation of cytokines. IL-6, in particular, seems to be a culprit. Cytokine analyses have shown a relation between higher peak levels of IL-6 and higher grades of CRS in CAR-T patients. It's characterized by a constellation of symptoms, which include fever, malaise, headaches, myalgias, and arthalgias and rigors with fever usually being the first symptom observed with CRS onset. Though it's time of onset can vary from a few hours to more than weeks post CAR-T infusion. In severe CRS, patients can have life-threatening hemodynamic instability, stemming from capillary leakage, hypoxia, coagulopathy, and organ dysfunction. Risk factors for severe CRS include high tumor burden, higher intensity of lymphodepletive chemotherapy prior to cell infusion, a higher level of administered CAR-T cell dose, and possibly also elevated inflammatory markers at baseline prior to infusion, such as abnormally high C-reactive protein and ferritin. Since high elevations of IL-6 were noted in the early CD19 CAR-T trial patients, administration of tocilizumab, a monoclonal antibody blocking the IL-6 receptor, was noted to demonstrate a rapid de-escalation of CRS symptoms. So now tocilizumab is actually a mainstay of treatment for CRS. Corticosteroids are also used in the treatment of CRS, especially if tocilizumab is not enough to curtail the symptoms. As I had already mentioned, earlier intervention with tocilizumab and/or corticosteroids did not appear to negatively impact CAR-T efficacy in clinical trials. Now, the second unique toxicity is neurotoxicity, which is now termed as Immune Cell Associated Neural Toxicity Syndrome, or ICANS for short. It can manifest as a tremor, impaired attention, difficulty writing, expressive aphasia, and confusion, but also can develop into more serious symptoms such as encephalopathy, delirium, stupor, and seizures. In rare cases, diffuse cerebral edema has developed, sometimes as a progressive crescendo, but occasionally also with very little preceding warning or clinical signs. ICANS can happen during CRS, but more commonly occurs after CRS, and can lag behind CRS by up to two weeks. Expressive aphasia is the most common characteristic symptom that develops first in patients before other symptoms, with the symptom progression taking anywhere from hours to days. Though cytokines leaking through a disruptive blood brain barrier is theorized as a possible cause of ICANS, its pathophysiology really remains largely unknown, and is a hot area of study currently. Unlike with CRS, treatment with tocilizumab does not lead to symptom benefit because tocilizumab does not cross the blood-brain barrier. So corticosteroids are really the only option for treatment of ICANS at this time. ASCO Daily News: So what's on the horizon for CAR T-cell therapies? Do you think they will be used to treat solid tumors in the future? Dr. Raghuveer Ranganathan: So far as the horizon and future directions for CAR T-cell therapies, there are already several modifications and upgrades being attempted to improve the current science and technology. One such enhancement is adding additional co-stimulatory intracellular domains to the actual CAR construct, a so-called "third generation" CAR-T. The idea is that by increasing that matter of costimulatory domains in the CAR construct, such as adding a CD28 costimulatory domain to the 4-1BB costimulatory domain that might be already present, there can perhaps be either amplification of signals within the CAR-T cells, and also harnessing of the different properties inherent to each different costimulatory domain, with augmented proliferation tumor cytotoxicity as a result. Currently, however, third-generation CAR-T constructs have yet to show better tumor cytotoxicity and better long-term remissions clinically, compared to second-generation constructs. Another enhancement is targeting two antigens simultaneously, or dual-targeting CAR0T. One of the purposes of this approach is to minimize tumor escape. Since the current second generation CAR T-cells target one cancer antigen at a time, if tumor cells were to down-regulate the expression of the targeted antigen, it would result in the tumor being able to evade recognition by the CAR T-cells. By targeting two antigens simultaneously, it's thought that the risk for tumor escape is lessened. A spinoff of dual-targeting CAR-T utilizes a sort of Boolean logic-gated approach where the CAR T-cells can be recalibrated to activate in an inducable fashion. In these logic-gated CAR T-cells, sensing of antigen 1 by a synthetic notch receptor within a modified T-cell then induces transcription and subsequent expression of a CAR receptor, which is specific for antigen number 2. Meaning that without binding of the antigen number 1 by our genetically-modified T cell, there is no expression of the CAR receptor binding to antigen number 2, which could help minimize on-target off-tumor toxicity. Another approach is called T-cells Redirected for Universal Cytokine Killing, or termed somewhat tongue-in-cheek as TRUCK T-cells, a playoff of CAR- T cells. These cells, in addition to direct tumor killing, also produce a pro-inflammatory cytokine, like IL-15 or IL-18, on coming into contact with a tumor, which helps to recruit a second wave of immune cells in a locally-restricted fashion, hopefully, to initiate a secondary attack on cancer cells, and also help enhance its own proliferation, cytotoxicity, and longevity. Now, there are unique obstacles and challenges for CAR-T and solid tumors that make it more difficult when compared to hematologic malignancies. Some of the existing challenges include overcoming the hostile tumor microenvironment, nutrient depletion, hypoxia, and inhibitory checkpoint molecule expression on solid tumors. Now, any one of these impediments would be a strong stumbling block to try and overcome, but when all of these hurdles occur together all at once, it can be very difficult to combat. In addition, on-target off-tumor toxicity is somewhat of a bigger challenge to overcome in solid tumors. And a likely cause for this is the overlapping antigen expression on epithelial tissues from which most solid tumor types originate. And also the spatial proximity and restriction of critical sites when targeting solid tumors. For example, a few years ago, a patient with metastatic colon cancer who had received CAR T-cell therapy as part of a trial died from acute respiratory distressive failure, with the cause thought to be low-levels of being expressed on lung epithelial cells. That said, I do believe CAR T can become a viable treatment modality in solid tumors with some modifications and improvements. One such method being tested in clinical trials is combining immune checkpoint therapy, such as PD-1 inhibitors, with CAR T-cells. Another possibility is to edit the native inhibitory receptor in CAR T-cells by switching out the inhibitory receptor's intracellular domain for an intercellular domain from a stimulatory receptor. For instance, we take the native PD-1 molecule from a CAR-T cell and edit or switch out the intracellular domain, and put in the intercellular domain from CD28. What you get now is a molecule which has the PD-1 receptor on the outside, but a CD28-signaling mechanism on the inside, so that the net result is actually positive for the CAR-T, which now gets added stimulus instead of inhibition. Such switch receptors are being incorporated into CAR T-cells to augment their activity and proliferation potential. And as I mentioned before, TRUCK T-cells and logic-based CAR T-cells are also other possible methods to conquering some of these obstacles posed by solid tumors. So while there's still much more investigation to be done in overcoming solid tumors, I do hope that we can make some strong headway in the near future. ASCO Daily News: Well, thank you Dr. Ranganathan for sharing your insights on CAR T-cell therapies with us today. Dr. Raghuveer Ranganathan: My pleasure. Thank you, Geraldine. ASCO Daily News: And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, please rate and review us on Apple Podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
with @OzAzamTmunity1, @JorgeCondeBio, and @omnivorousreadCAR T therapy, the groundbreaking new medicines that uses engineered T-cells to attack cancer, has been so effective in childhood leukemias that we believe it may actually be a potential cure. But this isn't just one new medicine, it's an entirely new therapeutic tool—and a total paradigm shift from most traditional medicines we've seen before.Tmunity CEO Usman "Oz" Azam was previously the head of Cell and Gene Therapies at Novartis, in many ways the first CAR T company and the team brought us blood cancer CAR T-cell therapy Kymriah—the first cell-based gene therapy to be approved in the US. In this conversation, Azam discusses with a16z's general partner Jorge Conde and Hanne Tidnam what CAR T therapy really is and how it all works. The conversation begins with the “patient and cell journey” of this treatment and how this medicine is developed, manufactured, delivered to patients; why exactly it's so different traditional medicines; what it will take to make these new medicines work on more kinds of cancer, scale to more patients, and cost less; and finally, what company building lessons can be learned from building the first CAR T company of its kind from the ground up.This episode was recorded at the annual a16z Summit.
A special interview with Dr Sophia Ononye as we discuss how AI, nanotechnology and social media can be used to foster collaboration between Big Pharma and the public. 2019 marked another remarkable year for the life science industry as evidenced by the surge in FDA approvals and M&A deals. Yet, for the increasingly discerning public, there is very little knowledge about these new therapies. The need for public education has never been so dire as a substantial proportion of new drugs are biologics with complex mechanisms of action that are often directed against rare, unknown diseases. Hopefully, the 2020s will mark a focal shift from patent cliffs to open collaboration between industry partners, between academia and the life science companies, and notably, between patients and the life science industry. If the 1990s or so-called “golden age of Big Pharma” was distinguished by blockbuster small molecules, the 2020’s will showcase niche-busters that are driven by the continued need for life science companies to maintain “first-in-class” or “best-in-class” status. Often, these niche-busters are developed for rare diseases with small patient populations and/or limited therapeutic options, which allows the manufacturer to charge higher prices for these drugs given little competition and a smaller patient population that is willing to pay for novel solutions. However, competition drives innovation and drug affordability. Starting probably with a bold move by Bristol Myer Squibb to focus its R&D efforts primarily on oncology, it seems that majority of the biopharmaceutical industry are hedging their bets in oncology. There are several reasons why this make sense. In particular, cancers are heterogeneous diseases that differ by tumor type and genetic profiles. Yet, if we use recent FDA approvals as a barometer, it is evident that the two most expensive CAR-T drugs, Kymriah and Yescarta, are for small patient populations. But the innovation behind these therapeutics is clouded by the fairly high price tags associated with them and limited understanding of pharmaceutical pricing dynamics. Sophia Ononye, PhD MPH MBA Read the full post here: https://sophiaconsultingfirm.com/f/role-of-technology-in-improving-reputation-of-the-life-sciences The Sophia Consulting Firm 186 Lenox Road, Suite 4B, Brooklyn, New York 11226 (347) 533-4578
Hvorfor sier Beslutningsforum nei til en genterapi som kan redde 20-30 norske liv? Vi snakket med Jan Anders Istad i Novartis som forklarer oss hvordan denne kompliserte prosessen fungerer.Beslutningsforum har sagt nei til to nye genterapier til voksne med lymfekreft. Den nye behandlingen, som kalles CAR T, ble utnevnt til "årets fremskritt" av den amerikanske kreftforeningen i 2017.Med oss i studio er Jan Anders Istad, leder for myndighetskontakt i Novartis. Novartis har forsket frem et av CAR T legemidlene som fikk avslag, den heter Kymriah. I løpet av episoden ringer vi også Kari Sandberg, leder av Lymfekreftforeningen og Harald Holte ved Lymfomavdelingen på Radiumhospitalet for å høre deres perspektiv på hvordan avslaget påvirker deres roller i Helse-Norge. See acast.com/privacy for privacy and opt-out information.
Topic Discussed : Global Cell Therapy MarketSpeaker: Aarti ChitaleKey Takeaways:This report covers the key trends and opportunities across the global cell therapy market. Some of the key areas being covered under the market include, industry trends, manufacturing automation, combination therapies and other future trends The report also highlights some of the emerging business models benefiting the market as well as the key drivers and restraints affecting the market growthWith the changing market landscape, Big pharma/bio-pharma players, are looking towards the adoption of a collaborative business approach by either entering into co-development/ co-commercialization agreements or acquiring smaller niche players so as to achieve competitive advantage with respect to specific therapy area or technologyAdditionally, in order to cater to the pricing needs of these high value therapies, the companies are adopting a pay for performance model which allows the payer to make a payment basis the therapeutic outcome of the novel therapyKymriah and yescarta are amongst the first such CAR-T cell therapies with this arrangement. Also, there is a large scale adoption of risk sharing, fast to market models, which supports the development of these novel therapiesFor further insights, please join us for future podcasts and become a member of Frost & Sullivan’s Leadership Council by emailing us at: digital@frost.com or click here to Contact Us.Related Keywords: Frost & Sullivan, Regenerative Medicine, Combination Therapies, Cell-Gene therapies, Stem Cell Therapies, Mesenchymal Stem Cells, Adipose Derived Stem Cells, Induced Pluripotent Stem Cells, European Medicines Agency, Food and Drug Administrations, Act for Safety of Regenerative Medicine, Pharmaceutical and Medical Devices Act, CRISPR/Cas9, ACR-T Cell Therapies, Kymriah, Yescarta, Gilead Sciences, Novartis, Mergers and Acquisitions, Genome Editing, Curative Therapies, Nano-medicine, Alternative payment Models, One-time Payment Model, Annuity Payment Model, Value Based Payment Model, Autologous Stem Cells, Allogeneic Stem Cells, Fast to Market Model, Risk Sharing Model, In-House Development, Competitive Playbook, Conditional Approval, Oncology, Neurology, Cardiovascular Diseases, Dermatology, Muscoloskeletal, ImmunologyWebsite: www.frost.com See acast.com/privacy for privacy and opt-out information.
ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2018 American Society of Hematology Annual Meeting, held December first through fourth in San Diego, California. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center, and Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. ASCO would like to thank Dr. Williams for discussing this topic. Dr. Williams: Hello. This is Michael Williams. I'm a professor at the University of Virginia Health System in Charlottesville, Virginia, and I'm reporting today on some exciting advances in lymphoma that were presented at the Annual Meeting of the American Society of Hematology, which was held in San Diego, California in early December 2018. Well, there were a number of areas of lymphoma that had important reports, and I'm going to just give you a small sampling of these today. We'll start with a new treatment option for patients with follicular lymphoma. Traditionally, this type of lymphoma, when it's symptomatic and needs therapy, the treatment of choice has been chemotherapy combined with a monoclonal antibody such as rituximab or obinutuzumab. But investigators, in a multicentered trial, decided to test whether you could use a chemotherapy-free treatment approach for patients like this by using rituximab combined with lenalidomide, which is also known as Revlimid, as a substitute for chemotherapy. And this is based on the fact that Revlimid plus rituximab has synergistic activity in patients with relapsed disease, so maybe we could see acceptable, high responses when it would be compared directly with rituximab plus chemotherapy. So the way the trial worked is this. Patients who needed therapy, who had advanced-stage follicular lymphoma—they had never had any therapy before—were randomized to either the rituximab-lenalidomide combination or a rituximab-chemotherapy combination that could include the regimens CVP or cyclophosphamide, vincristine, prednisone, the same combination given with daunorubicin, or the CHOP regimen, or rituximab combined with bendamustine. So over 1,000 patients were treated in this multinational study and the goal of the treatment, of the study was to prove that, actually, the ritux-lenalidomide was superior to the chemotherapy regimens. So the results showed, not superiority, but comparability. The complete remission rate between rituximab-len and ritux-chemotherapy were really identical, 48 and 53 percent, and the 3-year likelihood that the patients were progression-free, so had had no recurrence of their disease, was identical as well: 77 to 78 percent. There was no difference in survival which was 94% at 3 years in both arms. The toxicities differed, however. There was more rash with the lenalidomide combination, whereas low blood counts and the need for growth factor support such as G-CSF was greater with chemotherapy. And it was also interesting that some of the traditional risk factors didn't seem to apply, as much, for lenalidomide. So what would be considered higher risk patients treated with chemotherapy, seemed to do somewhat better with the lenalidomide combination. The importance for a patient with untreated follicular lymphoma who needs therapy is that a chemotherapy-free approach with rituximab plus lenalidomide can be considered equivalent to rituximab-chemotherapy. It’s worth discussing this with your oncologist when you're considering what treatment to use initially. The next subtype of lymphoma that I want to discuss is diffuse large B-cell lymphoma, and there's 2 presentations that I'm going to summarize. One, in patients with advanced stage disease, meaning stage III or IV. This identifies patients who have disease both above and below the diaphragm, to make it stage III, or stage IV means they've got bone marrow or other sites of involvement such as liver or bone. And the question being asked in this trial, which was part of the International GOYA trial, will take just a moment to explain. So the original GOYA trial compared whether a newer form of anti-CD20 monoclonal, namely obinutuzumab, which is also called Gazyva, how that would compare with the standard established monoclonal antibody, rituximab. And the initial findings of this study found that there was no benefit for the newer antibodies. So rituximab and CHOP chemotherapy was equivalent to obinutuzumab and CHOP chemotherapy in overall outcomes. But there was an opportunity with this trial to answer a question that's been out there for many years, and that is how many cycles of treatment does one need? So the investigators took advantage of this large study which included 712 patients who were randomized to rituximab plus CHOP. Just over 500 of them received 6 cycles, and the remaining 186 received 8 cycles. Even the patients who got 6 cycles of CHOP chemotherapy also got an additional 2 doses of rituximab, so the immunotherapy monoclonal antibody was equivalent between the 2 arms. And the results of this showed that there was really no difference at all with a followup of about 3 years. Response rates were equivalent and there was no difference in the patients staying in remission. It didn't matter in terms of survival which was excellent in both arms. There was, however, more toxicity in patients who received 8 cycles, including cardiac problems, infections, etc. These results showed that, I think we can finally put to rest the use of 8 cycles of rituximab-CHOP chemotherapy for advanced-stage large cell lymphoma. It's been an unknown entity because we never had a direct comparison of these. So we can now say that 6 cycles plus the additional 2 doses of rituximab is a standard for advanced-stage diffuse large B-cell lymphoma. Now, what about patients who have limited-stage, so stage I or II diffuse large cell lymphoma? That means just a single lymph node area's involved or 2 adjacent lymph node areas. In the past, these were treated either with 6 cycles of rituximab-CHOP or sometimes cycles of R-CHOP plus local radiation therapy. And in this study, which took a long time to complete; it began in 2005, but it enrolled 592 patients who were then randomized to either 4 cycles or 6 cycles of treatment. Radiation therapy was not planned for any of these patients except for very specific locations of involvement such as testicular DLBCL where radiation therapy is a standard. So the take-home message after over 5 years of follow-up for patients on this study showed that 4 versus 6 were identical. So 89% of patients were still in remission at 3 years after completing treatment, and the overall survival was really impressive, 98 to 99 percent in the 2 arms. So there was no benefit with limited-stage favorable disease. Now, who are these patients? So younger than age 60, stage I or II disease, and normal LDH. They did not have bulky disease, meaning there was no nodal mass more than 7 and a half centimeters. So if you fit those criteria, then you can benefit from a de-escalation of treatment and be spared the additional 2 cycles of R-CHOP. Now, sticking with the topic of diffuse large B-cell lymphoma, a challenging problem in our field is for patients who relapse after their initial therapy, or in some cases, fail to respond to a treatment like rituximab-CHOP or an equivalent immuno-chemotherapy regimen. And a very exciting advance in the field, over the past few years, has been the development of chimeric antigen receptor T cells or CAR Ts. Traditionally, what we've done with patients who relapse or have resistant diffuse large cell lymphoma is to give them a second-line, high-dose chemotherapy regimen, and if they showed a good response to that, they could then go to a dose-intensive treatment with a follow-up consolidation by autologous stem cell transplantation. And with that, you can cure, overall, about 40% or so of patients. The CAR T-cell approach takes a very novel immunotherapy effort, and that is that a patient's own T-cells are removed from the peripheral blood, and then in the laboratory, they're modified and reprogrammed so they can attack the patient’s diffuse large B-cell lymphoma cells that are resistant to chemotherapy. So there were 2 important follow-up studies, each of them involved 1 of the agents, the CAR T-cell products, that are approved by the Food and Drug Administration for patients with relapsed or refractory diffuse large cell lymphoma. The first used the CAR T known as axicabtagene ciloleucel. It's quite a complex name, but it goes by the abbreviation of axi-cel or the trade name is Yescarta. So in this study, the investigators wanted to show that this is a treatment that can be extended to many centers with the product, the CAR T being made in a central facility by the pharmaceutical company. So it was a retrospective study of 295 patients at 17 international centers: a lot of patients across a broad spectrum of sites in North America and Europe. Virtually all the patients were able to develop and obtain a CAR T product. It included patients with some of the higher risk forms of the DLBCL such as double and triple-hit lymphoma. About 3% of patients died during the treatment, although only 1% of these were felt to be related to the treatment itself. The response rates were quite good, with about 80% of people responding. The complete remission rates at 30 days after the CAR T infusion were 47%. So it proved that you can use this centrally manufactured product. So the patients T-cells are collected at the local center, they're shipped to the manufacturing facility, the CAR Ts are generated, sent back to the home institution, and then infused. And I'll say a word in a moment, after I introduce the next paper, to explain some of the side effects of this treatment. So the second study was also presented at the ASH meeting and published simultaneously in the New England Journal of Medicine in early December 2018. So this used the second FDA approved CAR T known as tisagenlecleucel or Kymriah. In this study, there were 93 patients who were able to receive a CAR T-cell infusion, 40% of them achieved a complete remission, and another 12% had a partial response. And that a year after their documented response, two-thirds of these patients were maintaining the response, including 79% of those who achieved a complete remission. So this trial again confirmed across multiple centers that CAR T-cells can be an effective therapy. The side effects of both of these drugs can include something called cytokine release syndrome where the immunologic effects, essentially, release cytokines into the blood that can mediate a capillary leak, respiratory troubles, and low blood pressures, that can, in some cases, require intensive care unit support. This can be managed by other mediators that tamp down the cytokine effect such as an interleukin-6 antagonist. The other toxicity which is less well understood and problematic can be neurologic effects which can include confusion, speech alterations and even coma. But again, approaches and treatments to identify and manage this are being developed. So CAR Ts have become established. They're available at a number of centers, but it's important to consider this as a treatment option in the setting of relapsed or refractory diffuse large cell lymphoma. The long-term curability is still unknown, although it's encouraging that patients with very resistant disease who'd get a good response can maintain that response out to a year and more. So we're going to be very interested to see how the longer-term follow-up comes together. The final topic I wanted to mention today is Waldenstrom macroglobulinemia. So this is a unique form of indolent B-cell lymphoma where the lymphoma cells release a monoclonal immunoglobulin into the blood known as IGM. Now, IGM is a very large antibody, and because of that, when the levels are very high, patients can have problems with high viscosity or thickening of the blood, which can cause confusion, vision changes, sometimes respiratory problems. And these patients also can become anemic or develop enlarged lymph nodes or enlarged spleen. So one of the standard treatments for this disease is, again, the immunotherapy monoclonal antibody rituximab, but the responses are typically incomplete and somewhat short-lived. So it was exciting, a couple of years ago, when the targeted tyrosine kinase inhibitor, ibrutinib, which targets the bruton tyrosine kinase in malignant B-cells. This is an agent that's approved in chronic lymphocytic leukemia, and certain lymphomas such as mantle cell, marginal zone, as well as lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. So here's the study. Investigators had shown that if you combine rituximab with ibrutinib, that the response rates were improved as compared with rituximab by itself. And in a follow-up study that looked at this over a longer period of time, these benefits of the combined therapy were confirmed. These included patients without prior treatment or with prior treatment, with either chemotherapy or rituximab. And there was a confirmed benefit for the ibrutinib-rituximab combination in patients, whether they had had treatment before or not, and regardless of certain genetic markers that we use to assess risk in Waldenstrom. It was also shown that because these treatments continue indefinitely, as long as patients are responding and tolerating therapy, that the response rates improved over time. The side effects of treatment with ibrutinib are well-known, now, after several years of use across a variety of diseases, as mentioned, and include diarrhea, sometimes rash. You can see problems with easy bruising or bleeding, atrial fibrillation, and sometimes skin rash, or muscle and joint aches. But most patients are able to continue therapy and to benefit from it over an extended period of time. So the combination of ibrutinib plus rituximab was shown to add benefit compared with rituximab alone, and again, is a treatment approach and option that you could consider whether you have previously untreated or relapsed Waldenstrom macroglobulinemia. So overall, it was a very exciting meeting. We've had practice-changing data presented, and I've given you just a sampling of those. I think it's important for anyone dealing with lymphoma, or related malignancy, such as CLL or multiple myeloma to be very encouraged by the progress in the field, the opportunity to get much better responses with less toxicity and with minimal or no use of traditional chemotherapy. So we're pleased to be able to offer these treatment approaches for our patients. And I thank you for your taking part in the podcast and hope you found it useful. Thanks again. ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.
The P4A team analyze Novartis' deal with Celluar Biomedicine Group to supply the CAR-T therapy Kymriah and the successes and failures of the reimbursement of Vertex's cystic fibrosis drug, Orkambi. Presenter: Max Rex Contributor: Nader Murad, Senior Analyst
Back from a summer break! The P4A team discuss the reasons behind NICE's rejection of Novartis' CAR-T therapy Kymriah, Denmark and Norway's joint drug purchasing agreement and US patient groups pushing back against ICER's influence in drug reimbursement. Presenter: Max Rex Contributor: Aparna Krishnan
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Menarini, Medineos, Iqvia, Novartis.Persone: Luca Li BassiNuove terapie: Kymriah, riluzolo.Patologie: Alzheimer, leucemia linfoblastica acuta, SLA.Lavoro: Clinical Research Associate, Clinical Reserach Associate - Site and Patient Access, Senior MSL - Internal Medicine.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Menarini, Medineos, Iqvia, Novartis.Persone: Luca Li BassiNuove terapie: Kymriah, riluzolo.Patologie: Alzheimer, leucemia linfoblastica acuta, SLA.Lavoro: Clinical Research Associate, Clinical Reserach Associate - Site and Patient Access, Senior MSL - Internal Medicine.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Bayer, Covestro, Simef, Icon, Sandoz, Novartis, Gilead, Incyte, Clinipace Worldwide, IQVIA.Persone: Marco Romano (Simef), Stefania Gori (Aiom), Georg Sawa (East Anglia University di Norwich).Nuove terapie: belimumab, Kymriah, Biktarvy.Patologie: tumore al seno, demenza, lupus eritematoso sistemico, depressione, leucemia linfoblastica acuta, HIV.Lavoro: Medical Science Liaison, Project Manager, Regulatory Affair Officer.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Bayer, Covestro, Simef, Icon, Sandoz, Novartis, Gilead, Incyte, Clinipace Worldwide, IQVIA.Persone: Marco Romano (Simef), Stefania Gori (Aiom), Georg Sawa (East Anglia University di Norwich).Nuove terapie: belimumab, Kymriah, Biktarvy.Patologie: tumore al seno, demenza, lupus eritematoso sistemico, depressione, leucemia linfoblastica acuta, HIV.Lavoro: Medical Science Liaison, Project Manager, Regulatory Affair Officer.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: EMA, Teva, Bayer, Menarini, Allergan, Repros Therapeutics, Novartis, FDA, Sanofi, Eli Lilly, Gilead, Kite Pharma, Ionis Pharmaceuticals, Roche.Persone: Jörg Reinhardt (Novartis), Franco Cavalli (Istituto Oncologico della Svizzera Italiana), Alberto Albanese (Humanitas).Nuove terapie: Kymriah, Admelog, Humalog, emicizumab, Yescarta.Patologie: infertilità, leucemia, diabete, emofilia A, linfoma non-Hodgkin, sclerosi laterale amiotrofica, tubercolosi, Còrea di Huntington.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: EMA, Teva, Bayer, Menarini, Allergan, Repros Therapeutics, Novartis, FDA, Sanofi, Eli Lilly, Gilead, Kite Pharma, Ionis Pharmaceuticals, Roche.Persone: Jörg Reinhardt (Novartis), Franco Cavalli (Istituto Oncologico della Svizzera Italiana), Alberto Albanese (Humanitas).Nuove terapie: Kymriah, Admelog, Humalog, emicizumab, Yescarta.Patologie: infertilità, leucemia, diabete, emofilia A, linfoma non-Hodgkin, sclerosi laterale amiotrofica, tubercolosi, Còrea di Huntington.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
Every week, The American Journal of Managed Care® recaps the top managed care news of the week, and you can now listen to it on our podcast, Managed Care Cast. This week, the top managed care news included coverage from the 59th American Society of Hematology Annual Meeting and Exposition; recommendations on the use of diabetes drugs with cardiovascular indications; and a new study found that despite changes in insurance plans to give consumers more clout, unnecessary medical spending remains a problem. Read more about the stories in this podcast: What We're Reading: Medical Device Approval; Medical Laboratories Sue Government; ACA Sign-Up Deadline: www.ajmc.com/newsroom/what-were-reading-medical-device-approval-medical-laboratories-sue-government-aca-signup-deadline CAR T Progress: Global Submissions for Kymriah, 42% Ongoing Response With Yescarta in ZUMA-1 Patients: www.ajmc.com/conferences/ash-2017/car-t-progress-global-submissions-for-kymriah-42-ongoing-response-with-yescarta-in-zuma1-patients- Dr Stephen Schuster Outlines CAR T Results Seen in Leukemia, Lymphoma, and Myeloma: www.ajmc.com/conferences/ash-2017/dr-stephen-schuster-outlines-car-t-results-seen-in-leukemia-lymphoma-and-myeloma American Society of Hematology coverage: www.ajmc.com/conferences/ash-2017 ADA 2018 Standards Address Drugs With CV Benefits, Hold Firm on Blood Pressure: www.ajmc.com/newsroom/ada-2018-standards-address-drugs-with-cv-benefits-hold-firm-on-blood-pressure Impact of Consumer-Directed Health Plans on Low-Value Healthcare: www.ajmc.com/journals/issue/2017/2017-vol23-n12/impact-of-consumerdirected-health-plans-on-lowvalue-healthcare
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Bayer, Loxo Oncology, ISS, EMA, Shire, FDA, Angelini, Aboca, AIFA, Novartis, Kite Pharma.Persone: Carlo Petrini (ISS), Francesco Scopesi (Shire), Oliver Mundell (GBI Research), Mario Melazzini (AIFA), Crystal Mackall (Stanford University School of Medicine’s Cancer Institute).Nuove terapie: Loxo-101, Loxo-195, pegaspargasi, Kymriah, Yescarta.Patologie: leucemia linfoblastica acuta, schizofrenia, diabete, epatite C, cancro.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Bayer, Loxo Oncology, ISS, EMA, Shire, FDA, Angelini, Aboca, AIFA, Novartis, Kite Pharma.Persone: Carlo Petrini (ISS), Francesco Scopesi (Shire), Oliver Mundell (GBI Research), Mario Melazzini (AIFA), Crystal Mackall (Stanford University School of Medicine’s Cancer Institute).Nuove terapie: Loxo-101, Loxo-195, pegaspargasi, Kymriah, Yescarta.Patologie: leucemia linfoblastica acuta, schizofrenia, diabete, epatite C, cancro.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
Acute lymphoblastic lymphoma is the most common childhood cancer, with about 3,100 patients younger than 20 diagnosed every year, according to the National Cancer Institute. Children’s Mercy contributed to the trial of the first U.S. approved cancer gene therapy, Kymriah, for children and young adults with acute lymphoblastic leukemia that is resistant to treatment or has relapsed. Doug Myers, MD, Children’s Mercy oncologist, was an early investigator of immunotherapy using chimeric antigen receptor t-cells to treat pediatric cancer and led the hospital’s participation in the Kymriah trials. Join us as Dr. Myers discusses immunotherapy, the science behind chimeric antigen receptor technology, and it significance for patients now and in the future.
This week, the top managed care stories included the end of the latest attempt to repeal the Affordable Care Act; a call to include the patient's voice in cancer quality metrics; and an argument for caution regarding the newly approved CAR T-cell therapy, Kymriah.
The TWiV team reviews the first FDA approved gene therapy, accidental exposure to poliovirus type 2 in a manufacturing plant, and production of a candidate poliovirus vaccine in plants. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Become a patron of TWiV! Links for this episode ASM Conference on Viral Manipulation of Nuclear Processes ASM Public Outreach Fellowship Kymriah approved (PennMed) CAR T cells (NCBI) Cost of Kymriah (NYTimes) Accidental exposure to poliovirus type 2 (Eurosurveill) GAPIII (WHO) Poliovaccine candidate in plants (Nat Commun) Vertical vaccine farm (TWiV 47) All picornaviruses, all the time (TWiV 425) Image credit Letters read on TWiV 459 This episode is brought to you by the Defense Threat Reduction Agency. Part of the U.S. Department of Defense, the Agency’s Chemical and Biological Technologies Department hosts the 2017 Chemical and Biological Defense Science & Technology Conference to exchange information on the latest and most dynamic developments for countering chemical and biological weapons of mass destruction. Find out more at http://www.cbdstconference.com Weekly Science Picks Kathy - Cassini photos Dickson - Caliber Biotherapeutics Alan - Grav Rich - Google street view of the International Space Station (article) Vincent - the bioinformatics chat Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Almirall, Sanofi, AstraZeneca, Takeda, Protein Sciences, Novartis, FDA, Intercept.Persone: Peter Guenter (Almirall), Donata Medaglini (Università di Siena).Nuove terapie: MEDI1341, Flublok, canakinumab, Kymriah, Ocaliva.Patologie: Parkinson, Ebola, ictus, infarto, leucemia linfoblastica acuta, colangite biliare primitiva.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple
PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Almirall, Sanofi, AstraZeneca, Takeda, Protein Sciences, Novartis, FDA, Intercept.Persone: Peter Guenter (Almirall), Donata Medaglini (Università di Siena).Nuove terapie: MEDI1341, Flublok, canakinumab, Kymriah, Ocaliva.Patologie: Parkinson, Ebola, ictus, infarto, leucemia linfoblastica acuta, colangite biliare primitiva.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/Hai un dispositivo Apple? Seguici e abbonati al podcast tramite la app iPod http://nelfarmaceutico.link/pharma-apple