Study of blood, the blood-forming organs, and blood diseases
Synopsis: Michelle Werner is the CEO of Alltrna and a CEO-Partner at Flagship Pioneering. Alltrna is the world's first tRNA platform company to decipher tRNA biology and pioneer tRNA therapeutics to treat thousands of diseases. Flagship Pioneering conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. Michelle discusses her 20+ year career in drug development and the importance of bringing new innovations to people who need them. She talks about her motivations behind going to business school in London and why she felt she needed to supplement her science and math education with the fundamentals of business in order to transition her career to commercial from R&D. She discusses tRNA as a treatment modality and its potential to be a platform technology. Finally, she shares where the company is from a development perspective and fundraising announcements. Biography: Michelle C. Werner is a seasoned pharmaceutical executive with more than 20 years in the industry spanning both commercial and research & development (R&D) responsibilities. Most recently, Michelle served as Worldwide Franchise Head, Solid Tumors at Novartis Oncology, where she was responsible for delivering the disease area strategies across multiple tumors and led business development efforts resulting in a doubling of long-term portfolio value for the franchise. Previous to Novartis, Michelle was a senior leader at AstraZeneca, where she held multiple positions during her five-year tenure. As Global Franchise Head in Hematology, Michelle was critical in launching multiple indications worldwide for CALQUENCE® and was responsible for developing the mid- and long-term strategy for AstraZeneca in hematology. Prior to this role, Michelle served as Head of US Oncology, where she led the business through dramatic growth in both team and revenue through eight-plus product launches as well as Country President for the Nordics and Baltics, where she also served as an elected Board Member to Sweden's pharmaceutical industry association. Previous to AstraZeneca, Michelle was with Bristol Myers Squibb for 10 years in various positions of increasing responsibility including roles in sales, marketing, and market access in the US and UK, and above market in Europe (based in France) and global almost exclusively in oncology. Michelle started her professional career in R&D, working hands-on with patients at the Oncology Clinical Trials Unit at Harvard Medical School before moving into industry in clinical operations. Outside of her corporate responsibilities, Michelle is a wife and mother to three children and is a member of the rare disease community. She is currently serving a Board appointment for the non-profit organization Rare Disease Renegades, a purpose that fuels her passions both personally and professionally. Michelle holds a B.A. in biology & anthropology from the University of Pennsylvania and an MBA from the London Business School (UK). She also completed an Executive Education program for Women on Boards at Harvard Business School in 2018.
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Dr. Akshat Jain, Director Inherited Bleeding Disorders at the Loma Linda University Children's Hospital, is here with a wide-ranging conversation, including gene therapy access and affordability in low resource areas. Plus, a new Elite Athletes segment featuring San Jose Sharks Head Coach, David Quinn and another installment of I'm Fine with a spotlight on–leadership. Be careful, leaders, we're coming for ya! Show Notes: Subscribe: The BloodStream Podcast Watch Redefining Impossible for free HERE Presenting Sponsor: Takeda, visit bleedingdisorders.com to learn more. Elite Athletes and I'm Fine segments presented by @Sanofi Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook BloodStream on Twitter
In this week's episode, we discuss real-world evidence for CAR T cell therapy in older patients with diffuse large B-cell lymphoma, inhibiting endogenous anticoagulant pathways in congenital factor deficiencies, and finally targeting the HSP90 epichaperome in acute myeloid leukemia.
Caris Precision Oncology Alliance Chairman, Dr. Chadi Nabhan, sits down with Dr. Tina Bhatnagar, Associate Professor, Director of Hematology and Medical Oncology at West Virginia University. Together they discuss disparities research, the types of methodologies used and what can be done to mitigate the disparities seen in practice. For more information, please visit: www.CarisLifeSciences.com/POA-Intro/
Steven Woloshin is a professor of medicine and the director of the Center for Medicine and the Media at the Dartmouth Institute and a member of the Dartmouth Cancer Center. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S. Woloshin and Others. The New USPSTF Mammography Recommendations — A Dissenting View. N Engl J Med 2023;389:1061-1064.
Video of this clip: https://mehlmanmedical.com/hy-usmle-q-860-hematology Main website: https://mehlmanmedical.com/ Instagram: https://www.instagram.com/mehlman_medical/ Telegram private group: https://mehlmanmedical.com/subscribe/ Telegram public channel: https://t.me/mehlmanmedical Facebook: https://www.facebook.com/mehlmanmedical Podcast: https://anchor.fm/mehlmanmedical Patreon: https://www.patreon.com/mehlmanmedical
In this week's episode, we'll discuss the findings from the final analysis of the CLL2-GIVe trial, learn how NOTCH2 mutants promote resistance to chemotherapy in diffuse large B-cell lymphoma, and discuss the role of DBY/HLA class II complexes in chronic graft-versus-host disease.
Dr Martin Hutchings from Rigshospitalet, Copenhagen University Hospital in Copenhagen, Denmark, and Dr Loretta Nastoupil from The University of Texas MD Anderson Cancer Center in Houston, Texas, discuss the current and future role of CD20 x CD3 bispecific antibodies in the management of non-Hodgkin lymphoma moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://researchtopractice.com/InsidetheIssue2023/NHL)
In this episode of the Balancing Chaos podcast, Kelley is joined by Dr. Sanjay Juneja, a triple-board-certified hematologist and medical oncologist. Shortly into his professional career, he became regarded as a seasoned thought leader for his media presence as the 'TheOncDoc', where he educates over half a million followers on cancer concepts and the latest therapies through relatable, entertaining content.In this episode, Kelley and Dr. Juneja discuss the importance of mindset and positivity in medical outcomes, highlighting the statistical difference in quality of life and survival for individuals with optimism, self-image positivity, and even prayer. Dr. Juneja also highlights the importance of educating patients with a cancer diagnosis in order to decrease levels of anxiety and to create an empowered path through treatment. Kelley asks Dr. Juneja to describe all of the different lifestyle factors from diet, to exercise, to stress and how each impacts the potential for a cancer diagnosis. Finally, the two talk through the future of cancer treatments and prevention. To connect with Dr. Sanjay Juneja, click HERETo connect with Kelley, click HERETo get 20% off Kelley's Health and Hormones Course + a FREE Lab Review click HERE and use code BALANCINGCHAOS20To get 10% off Kelley's WBK method app with your annual membership, click HERE and use code BALANCINGCHAOS
In this week's episode, we'll learn about long-term outcomes with pembrolizumab in relapsed/refractory classical Hodgkin lymphoma. Next, what's behind the accumulation of toxic free alpha-globin in beta-thalassemia? Finally, a road map for managing CAR T cell hematologic toxicity.
My guest today is a native Texan, avid outdoorsman and entrepenuer. Ty Henrich, founder of Two Dove Outdoors, stops by to talk about the origin of Two Dove and what to come. Learn more about Two Dove Outdoors at www.twodoveoutdoors.com on Instagram @two_dove_outdoors and find them in-store at our Willow Park shop or our flagship location in the heart of downtown Abilene.September is Child Cancer Awareness Month and we partner with Cook Children's in their #EraseKidCancer Campaign in hopes of finding a cure. All month long, all proceeds from our LSDG Branded Hats as well as our #EraseKidCancer Collection are donated to Cook Children's and earmarked for Hematology & Oncology.
Since arriving at Children's of Alabama in 2019, Girish Dhall, M.D., has worked to get the hospital involved in more research consortia. In this episode, Dhall explains the role of consortia, how they're helping Children's patients and how they're enabling the hospital to make a global impact.
We are thrilled to introduce our newly rebranded video podcast— 'Better Today, Healthier Tomorrow – an Arkansas Children's Podcast.' The name reflects our mission of a healthier future for the children of Arkansas and beyond.We couldn't think of a better way to launch than sitting down with Arkansas Children's President and CEO, Marcy Doderer, who is celebrating a decade of serving the state's only pediatric health system. Doderer reflected on what she's most proud of during her tenure at AC Arkansas Children's, her experience on the “parent side of the bed,” and its impact on her leadership style. She also revealed that being president and CEO was not her first job at Arkansas Children's — as a teenager, she worked in the billing department, converting paper files to microfiche.
In this week's episode, we'll learn more about the treatment of relapsed and refractory cutaneous T-cell lymphoma with dimethyl fumarate, discuss the use of lipid nanoparticles for ex vivo editing of human hematopoietic cells, and learn more about racial and geographic disparities in lymphoma clinical trials.
Blood associate editors Jeanne Hendrickson and Thomas Ortel edited a How I Treat series on inpatient consultative hematology. In this timely series of articles, the authors present an approach to bleeding, thrombosis, anemia, and quantitative neutrophil abnormalities.
In this session, It will seek to help guide you on how to respond to God’s Command and Commission, The quest for discovering and following God’s will and purpose for one’s life is often an illusion to many children of the Living God, Many believers resorts to imitating others and or live a hypocritical phantom life as they are tied down to daily engagements and undertakings of everyday life, It is hoped that discovering the reason for living your life with purpose is made easier. You will discover the purpose for which God design you and gain the confidence to fruitfully be where you belong, through the power of the Holy Spirit. You will be guided through a biblical process and principles to seeing exactly God’s intent for your unique being and person, as Gods design, where you will discover that It all began with God before the foundations of the earth. Ever since, before the fall of humanity, God has you in mind, and he designed you for a purpose and through a process, but as a result of the departure of humans from God, through disbelief, you became blind and were kept ignorant of His plans for you. However, you will discover that His Deep love and Great Mercy, God called you to salvation, you became a new creature and adopted as His Child, hence He qualified you, by being a new creature in His image, He desires for you to return and rediscover His plan and purpose for your life As He God Intended. Responding to Gods Command and Commission, is a call to be ready, Dressed for service fully equipped and Lacking in nothing as you Respond through Obedience, based on a biblical Principles, These herculean task by helping you identify your uniqueness within the body of Christ, and to enable you walk confidently and victoriously where you belong in the program of God through the enabling power of the Holy Spirit. Finally, through the Scriptures and the Power of the Holy Spirit, You will be exposed and guided to God’s Command and Commission, That you begin to instantly manifest the reality of your purpose for living, Emblemed and empowered with full of Zeal, Passion and Fruitfulness, Genuinely ready for all the good works God has designed you to accomplish – Loving God with all your heart, soul and strength and loving others through your service of obedience to his Commission, Praying, Evangelizing, Discipling, Equipping and living a lasting fruit to the Glory of God. Our focus will be what it does take to be dressed, ready for service from your call to salvation to your call to service, Exploring your Meditational life, Family Life and a life of Obedience to His Command and Commission. AS YOU RESPONDING TO GOD’S COMMAND AND COMMISSION
Featuring a slide presentation and related discussion from Dr Jeremy Abramson, including the following topics: Long-term follow-up data with Bruton tyrosine kinase (BTK) inhibitors as monotherapy for chronic lymphocytic leukemia (CLL): The CLL12 and SEQUOIA trials (0:00) Extended follow-up results with venetoclax combined with anti-CD20 antibodies or a BTK inhibitor for CLL: The CLL14, MURANO and GLOW trials (5:27) Primary analysis of the TRANSCEND CLL 004 trial evaluating lisocabtagene maraleucel for relapsed/refractory (R/R) CLL (12:40) Genomic evolution and resistance to pirtobrutinib in patients with covalent BTK inhibitor-pretreated CLL in the Phase I/II BRUIN study (16:24) Chimeric antigen receptor (CAR) T-cell therapy data with axicabtagene ciloleucel and lisocabtagene maraleucel for R/R follicular lymphoma (FL) (18:24) Bispecific antibodies as treatment for R/R FL: mosunetuzumab, epcoritamab, odronextamab and TNB-486 (22:57) Novel treatment approaches for mantle cell lymphoma (MCL): First-line acalabrutinib/rituximab and lisocabtagene maraleucel for R/R disease (32:54) Updated results from studies evaluating loncastuximab tesirine, such as LOTIS-2, and CAR T-cell therapy, such as TRANSFORM and ZUMA-7, for R/R diffuse large B-cell lymphoma (39:29) Ongoing follow-up from pivotal trials of bispecific antibodies for large B-cell lymphomas (46:01) SWOG-S1826: Results from the Phase III trial evaluating nivolumab with doxorubicin/vinblastine/dacarbazine (AVD) versus brentuximab vedotin with AVD for advanced-stage classic Hodgkin lymphoma (51:48) CME information and select publications
Dr Jeremy Abramson from Massachusetts General Hospital in Boston discusses key presentations on chronic lymphocytic leukemia and lymphomas from recent oncology/hematology conferences.
Featuring an interview with Dr Jeremy Abramson, including the following topics: Choice of Bruton tyrosine kinase (BTK) inhibitor as first-line therapy for chronic lymphocytic leukemia (CLL) (0:00) Perspectives on the use of chemoimmunotherapy versus BTK inhibitors as front-line treatment for CLL (2:31) Chimeric antigen receptor (CAR) T-cell therapy-associated ICANS (immune effector cell-associated neurotoxicity syndrome) and infectious complications in patients with CLL (6:21) Available data with bispecific antibodies for CLL (9:38) Sequencing CAR T-cell therapy and pirtobrutinib for patients with previously treated CLL (11:09) Integrating bispecific antibodies into community-based practice; strategies for mitigating associated toxicities (14:25) CD20 versus CD19 as a therapeutic target in lymphomas (20:31) First-line treatment selection for patients with mantle cell lymphoma (23:07) Chemotherapy combined with nivolumab or with brentuximab vedotin as initial therapy for Hodgkin lymphoma (30:12) CME information and select publications
Dr Jeremy Abramson from Massachusetts General Hospital in Boston discusses key presentations on chronic lymphocytic leukemia and lymphomas from recent oncology/hematology conferences. CME information and select publications here (https://researchtopractice.com/OncologyTodayPostConf23/CLLLymphoma)
In this week's episode, we'll review a detailed safety profile of acalabrutinib versus ibrutinib in patients with previously treated chronic lymphocytic leukemia, discuss a report that leukocyte inflammation contributes to trauma-induced coagulopathy by oxidation and degradation of fibrinogen, and finally, discuss a pharmacokinetic-pharmacodynamic analysis that shows higher abatacept exposure decreases occurrence of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor.
Dr Hans Lee from The University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr Saad Zafar Usmani from Memorial Sloan Kettering Cancer Center in New York, New York, discuss approved and novel bispecific antibodies and their current and potential roles in the treatment of multiple myeloma. CME information and select publications here (https://www.researchtopractice.com/InsidetheIssue2023/MM).
Dr. Björn Mellgård, VP and Global Program Lead of rare genetics and hematology at Takeda, is passionate about finding a cure for cTTP, congenital thrombotic thrombocytopenic purpura. This ultra-rare disease, caused by an enzyme deficiency, presents in early childhood and results in life-threatening blood clots. With their investigational drug TAK-755, a recombinant enzyme, the volume is very small, and the infusion takes four to five minutes and is a replacement therapy to allow patients to avoid daily symptoms and acute episodes. Björn explains, "What happens then is that we have our coagulation system, and many people have heard about bleeding disorders, mainly probably hemophilia, where you lack certain factors which are important to make the blood clot. TTP is on the other side of the spectrum, and the deficiency we're talking about, this ADAMTS13 enzyme, is also importantly involved in blood coagulation." "But the effect is when you don't have this enzyme present. The blood has a tendency to spontaneously form blood clots in the circulation. And these blood clots then tend to lodge in critical organs such as the brain, the heart, and the kidney, and the patients then suffer symptoms based on that." "So, our drug then represents a recombinant enzyme. So, it's a recombinant protein that is produced in a laboratory. It's exactly the same as we have in our bodies. And this kind of replacement therapy has been used for a long time. And I mentioned hemophilia as an example where Takeda and also other companies have recombinant factor VIII in that case. So, the principle behind this treatment is to give the patient what they're missing. That's pretty straightforward in some sense." #Takeda #cTTP #TAK755 #RecombinantEnzyme #RareDisease Takeda.com Listen to the podcast here
Dr. Björn Mellgård, VP and Global Program Lead of rare genetics and hematology at Takeda, is passionate about finding a cure for cTTP, congenital thrombotic thrombocytopenic purpura. This ultra-rare disease, caused by an enzyme deficiency, presents in early childhood and results in life-threatening blood clots. With their investigational drug TAK-755, a recombinant enzyme, the volume is very small, and the infusion takes four to five minutes and is a replacement therapy to allow patients to avoid daily symptoms and acute episodes. Björn explains, "What happens then is that we have our coagulation system, and many people have heard about bleeding disorders, mainly probably hemophilia, where you lack certain factors which are important to make the blood clot. TTP is on the other side of the spectrum, and the deficiency we're talking about, this ADAMTS13 enzyme, is also importantly involved in blood coagulation." "But the effect is when you don't have this enzyme present. The blood has a tendency to spontaneously form blood clots in the circulation. And these blood clots then tend to lodge in critical organs such as the brain, the heart, and the kidney, and the patients then suffer symptoms based on that." "So, our drug then represents a recombinant enzyme. So, it's a recombinant protein that is produced in a laboratory. It's exactly the same as we have in our bodies. And this kind of replacement therapy has been used for a long time. And I mentioned hemophilia as an example where Takeda and also other companies have recombinant factor VIII in that case. So, the principle behind this treatment is to give the patient what they're missing. That's pretty straightforward in some sense." #Takeda #cTTP #TAK755 #RecombinantEnzyme #RareDisease Takeda.com Download the transcript here
Dr Kerry Rogers from the Ohio State University in Columbus, Ohio, discusses the education and care of patients with chronic lymphocytic leukemia. NCPD information and select publications here (https://www.researchtopractice.com/ONS2023CLLReview/InterviewAudio)
In this week's episode, we'll discuss pembrolizumab after autologous stem cell transplantation in patients with peripheral T-cell lymphoma. Newly reported phase 2 study results show that blocking PD-1 with pembrolizumab had a favorable safety profile and demonstrated promising activity, supporting further confirmatory studies in this setting; germline genetic predisposition to myeloid neoplasms in patients with hypoplastic bone marrow. Researchers report mutations that are significantly associated with cytopenias in adulthood in these patients. And pathogenic or likely pathogenic variants were linked to severe cytopenias and advanced myeloid malignancies; and finally, if monocytes and their descendants are less plastic than previously thought. Investigators have identified four functionally specialized monocyte subsets that derive from specific myeloid progenitor lineages. They show that the fate of these monocyte subsets is epigenetically scripted, with little flexibility after differentiation begins, even under conditions of stress.
George Weiner, MD, is a Professor of Hematology and Medical Oncology at the University of Iowa. Dr. Weiner has also served as the Director of the Holden Comprehensive Cancer Center for over two decades. He is also the CE Block Chair of Cancer Research at the University of Iowa Health Care and provides all oversight to cancer research at the cancer center. Dr. Weiner runs a research lab focusing on novel approaches to cancer immunotherapy. In honor of Dr. Weiner's service, the institution has announced an award named ‘The George Weiner Cancer Control Visionary Award'. When paralyzed with a life-changing decision, how often do we take a step back and let the critical thinker inside us reign free? To really analyze the situation and understand its outcomes on a larger scale? In today's episode, Dr. George Weiner shares a secret formula for making complex decisions in a split-second with the promise of the most successful pay-offs. To learn this “P.A.U.S.E.” protocol, tune in for more. Pearls of Wisdom: 1. There are people who can have the same goals but come from very different backgrounds and perspectives, and if we really work hard to understand where they're coming from, it makes it much easier to identify the joint goals because there are different approaches that can be successful towards the same goal. 2. We shouldn't let the lingo get in the way when communicating with peers or patients. We tend to use terms we understand very well, but others don't know what we're talking about. Everyone's capable of understanding very complex issues if we use terminology that they can understand. 3. Before we make any decisions. we should “P.A.U.S.E.” and look at it from different angles to try and think about what or how that would impact other people before executing it.
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Don't worry, Amy was given only 3 minutes to share her experience of The Eras Tour and then we get to the good stuff! Maya Bloomberg, the @TheHemeNP, shares four specific pillars of successful disclosure and we debut our new segment, I'm Fine. This new segment aims to challenge our “normals” and truly consider the possibilities. Show Notes: Subscribe: The BloodStream Podcast Presenting Sponsor: Takeda, visit bleedingdisorders.com to learn more. I'm Fine presented by @Sanofi Take a deeper at LevelsMatter.com. Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook BloodStream on Twitter
Drs. Vamsi Velcheti, Taofeek Owonikoko, and Janakiraman Subramanian discuss their experiences navigating the cancer drug shortage in the United States, the impact on patients and clinical trial enrollment, lessons learned, and proactive strategies to mitigate future crises. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone. On today's episode, we'll be discussing the impact of the shortage of cancer chemotherapy drugs across the United States. This has been affecting several thousands of patients with adult and pediatric cancers and hampering enrollment in clinical trials. Among the shortages are very commonly used drugs like cisplatin, carboplatin, methotrexate, and fludarabine. Some of these shortages have persisted since the time of the pandemic in 2020. So today, to discuss this really troubling scenario, I have two outstanding colleagues, Dr. Janakiraman Subramanian, the director of thoracic oncology at Inova Schar Cancer Institute in Virginia, and Dr. Taofeek Owonikoko, a professor of medicine and the chief of the Division of Hematology and Oncology at the University of Pittsburgh Hillman Cancer Center in Pittsburgh. Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod. So, a recent survey by the NCCN found that 90% of the nation's largest cancer centers have experienced a shortage in carboplatin, and 70% of the centers have reported a shortage in cisplatin. These are platinum-based chemotherapies we use frequently in patients with cancer, and these are often curative intent treatments for several cancers, and these are used in several tumor types, both solid tumors and hematologic malignancies. So, the scale of the problem is immense. Dr. Owonikoko, I'd like to hear your take on this situation and how are you dealing with this at the UPMC Cancer Center. Dr. Taofeek Owonikoko: Yeah, thank you, Dr. Velcheti, and happy to be part of this panel. As you rightly surmised, the chemotherapy drug shortage is what we've all experienced across the length and breadth of the United States. Our cancer center here in Pittsburgh is not an exception. We've had to be proactive as well as think outside the box to be able to manage the challenge. Just like every other cancer center across the country, maybe to varying degrees, we've had to look at patients in need of chemotherapy with these standard-of-care agents such as cisplatin or carboplatin, and to some degree docetaxel, during this past episode of drug shortage that we all went through. And while we did not have to, fortunately, cancel any patient treatment, we all went through it with bated breath; not sure of where the next batch of chemotherapy drugs will come through, but I would say in the past couple of weeks, we've actually seen some improvement in drug availability. But before then, we've had to have contingency plans where, on a weekly basis, we review our patient list and the drug regimens that they're going to need, and must make sure that we have enough drug on hand for those patients. And in situations where we thought we might not have enough drug; we also had a plan to use alternative regimens. We were proactive in having guiding principles that are consistent with ASCO's recommendations in terms of quality care delivery for cancer patients. So, I'm sure that this is more or less the same approach adopted by other leading cancer centers across the country. Dr. Vamsi Velcheti: Thank you, Dr. Owonikoko. And Dr. Subramanian, you're in a community setting, a large cancer center that serves a lot of patients in the state of Virginia. So, what is the scale of the problem at your institution and how are you handling it? Dr. Janakiraman Subramanian: First of all, Dr. Velcheti, thanks for having me here on this panel. And as you rightly said, this is a significant problem, and it is across the country like Dr. Owonikoko said. And as medical oncologists, we are not always thinking of drug shortages. Our focus is on taking care of our patients. So, this is one more issue that we need to keep in mind now as we manage our patients with cancer. When this shortage started, the biggest problem, as you know, was when we became aware of this was primarily in cisplatin and we had some of our patients who were getting curative treatment and we had to make a decision - can they get cisplatin or can they get carboplatin. And one of the things we did was to have an ethics committee that will review each patient that is being planned to receive cisplatin-based chemotherapy and come to a decision on how best we can support them. The template for some of this was based upon some of the triage mechanisms we used during COVID, as well as the ASCO guideline document for managing this chemotherapy shortage, which was one of the blueprints we used. And they have reviewed all cases, all patients that are being planned for cisplatin or carboplatin for that matter, and we come to a decision based on that. And we also have another committee that constantly monitors drug availability on a weekly basis and tries to forecast where the next problem would be as we take care of our patients. And particularly as a lung cancer doctor, we've had situations where we had to use carboplatin instead of cisplatin and even we also have carboplatin shortage. And so, the committee usually approves two cycles at a time, but thankfully so far we have not had a situation where we could not offer our patients the chemotherapy treatment. But we are very carefully monitoring the situation, hoping that this will improve. The other aspect of the shortage has been in 5FU. A lot of our GI colleagues; I treat esophageal cancer patients as well, where we've had to forego the bolus 5FU and have a 10% reduction on all 5FU infusions. And we've been using some of that dose reduction to ensure that we can have 5FU available for all our patients. And that's how we've been trying to manage this shortage situation here at Inova Schar. Dr. Vamsi Velcheti: Dr. Subramanian and Dr. Owonikoko, we are oncologists, we are treating patients, and the toughest part really is telling a patient that we don't have access to certain drugs and we have to switch treatments to perhaps another treatment regimen that may be suboptimal. And it's always a very anxiety-provoking discussion, and especially for patients with metastatic cancer, they're already under a lot of stress and it's a really difficult conversation. How do you handle that, Dr. Owonikoko? Dr. Taofeek Owonikoko: That's a conversation we all hope we don't have to have. And fortunately, with this current crisis, I've actually not had such misfortune of having to inform a patient that we don't have drugs to treat them or that we have to switch to something inferior. But conceptually, it's possible that could have happened and that would have been very difficult. But the one thing that we did, though, as part of our mitigation strategy was actually to inform the patient ahead of time because the way we handled this was to look at our inventory on a week-by-week basis. And if there are patients where we felt maybe they will be coming in towards the end of the week and we may not have enough drugs for them, to let them know the possibility exists that we might have to switch them to something different. While we did not have to do that for any patient, yes, there are patients that we had to give that heads up to, to say, “We're having this shortage. We're doing everything we can to make sure it's available. But just in case it's not available…” I think what is most important for most patients is to be aware of that decision ahead of time, to be able to process it, and to be transparent. The other challenge that we face was, if you have to choose between patients, what should be your guiding principles as to who gets the drug and who doesn't get it? I think it's very easy for all of us to say, “Oh, if it's curative intent, we do it. If it's not curative intent, we don't do it.” It's a little more complicated than that because if we put the equity hat on, curative intent doesn't actually mean that that life is more valuable than somebody who cannot be cured. And this is where really, I think having people with expertise in ethics of care delivery and disaster management will be very important for us to proactively anticipate that, should this become a recurrent problem in the future that we actually have a well-vetted approach, just like we did during COVID where you have to ration resources that we have those people with expertise to help us as oncologists because not all of us, at least personally I can speak for myself, that is not my area of expertise and comfort. Dr. Vamsi Velcheti: Excellent points. Dr. Subramanian, anything to add? Dr. Janakiraman Subramanian: Oh, absolutely. I echo what Dr. Owonikoko said. These are conversations that we would like to hopefully never have with our patients. But this is a crisis that we are facing now. And personally, I can tell you two situations where we ran into this problem. But overall, though, we never had to stop a treatment or cancel a treatment for our patient. In the first situation, we had a young man with a rare germ cell tumor in the hospital for whom cisplatin was key. He was already in the ICU and sometimes the treatment start dates are not perfect, unlike what we do in the outpatient setting, depending on how well he's doing or the treatment start dates might move by a day or so. So we basically had to hold a certain dose of cisplatin for him. This brings the next question, which is how do we decide who gets cisplatin versus who can go for an alternative option? And I think Dr. Owonikoko made a great point where, just because it is a curative disease does not mean their life is more valuable. This is where I think trying to make that decision at an individual level, as an individual treating physician can be extremely hard. And that's why at our institution we have this ethics committee where we have oncologists, pharmacists, and ethicists that review these chemotherapy orders, particularly for cisplatin, and try to use some guiding principles that we learned from COVID as well as ASCO's guidance to decide how we assign our resources. That's one option, one way we have done it. And then in another situation that was faced by one of my GI oncology colleagues was a patient that was originally planned to go on a clinical trial where the chemotherapy backbone was FOLFOX and because we had the 5FU shortage, we could not offer that patient clinical trial enrollment. And that was a tough conversation where they had to tell them that they could not go on a clinical trial that they were looking forward to. And this then brings the next question, which is by foregoing the bolus 5FU and by the 10% reduction in the infusional 5FU, are we providing them inferior treatment? And it's a conversation that's had at a very individual level. I don't envy my colleague who had to have that conversation. It's a challenge and we try to do our best to communicate to our patients that we are trying to provide care without trying to compromise the effectiveness of treatment for them. Dr. Vamsi Velcheti: Thank you so much both of you. And we had the same issues here at NYU in New York City as well. It appears, you know, the degree of shortage and the drugs that are in shortage has been somewhat different at different locations across the United States. But the theme has been that we are having to ration treatments for our patients. And of course, there are some tumor types where there's really no adequate substitution, for example, GU cancers. I mean, you can't really not give them cisplatin. A lot of these are situations which have curative intent and young patients. So, it's really troubling. And I think one of the things that really came out of this is there's been a lot of push from professional societies that actually ASCO has been spearheading and some intense discussions with CMS and legislators to kind of provide more long-term fix for these things. And I think all of us have to be more engaged in those discussions with our professional societies like ASCO to kind of help promote awareness. So if you kind of think about it, these drugs are not that expensive. These are generic drugs that we've all been using for such a long time. And the fact that we can't provide these drugs for various reasons is kind of really concerning. We spend so much money on research and more expensive drugs and not being able to manufacture these drugs within the country and kind of having to rely on complex supply chains is troubling, and I hope the situation improves very soon. So, I know both of you are at large cancer centers that enroll patients on clinical trials. Of course, these drugs, especially carboplatin, for lung cancer, especially, are like core treatments that are used in managing cancer patients with lung cancer. So how is this affecting your clinical trial accrual? Are you prioritizing patients on clinical trials for these drugs? Have you had to make any decisions to hold clinical trial accrual for certain trials? Kind of curious to hear. Dr. Taofeek Owonikoko: Yeah, so I can maybe weigh in a little bit on that in terms of what we've had to do for patients receiving treatment as standard of care versus those going on clinical trials. As we all recognize that when a patient goes on a clinical trial, even if they are going to receive a standard-of-care regimen as part of that trial, it still has to be administered in line with the protocol. So, during the extreme period of shortage anxiety, we actually had consideration for perhaps not putting patients on trial if we're not sure that they will be able to continue to receive the protocol-mandated treatment, whether it's a control intervention or the experimental intervention. The good thing to come out of this is at least here at UPMC, we actually did not have any instance where we had to deny a patient clinical trial participation. But there were anxious periods when we already had patients enrolled and they were scheduled to receive a platinum-containing regimen and we were not sure whether or not we were going to have adequate supply of the drug for them while on trial. I think this really raises an important consideration going forward as we come out of this current shortage. I don't by any stretch of the imagination assume that this is going to be the last one we experience, but I think the lessons learned here, we have to also carry that forward both in the design of the trial as well as in the regulatory environment surrounding clinical trial conduct, to say, should another incidence of drug shortage are to happen, how do we actually operationalize that with respect to patients on trial, whether starting or already on trial? I think it's much more challenging when the patient is already on the trial, they've already started. It's less challenging if you just have to make a decision about somebody starting newly on the trial. But equally important is that by not allowing new patients to go on trial is denying something that potentially could be of benefit to them, albeit it is still a trial, it's not an established treatment option yet. Dr. Janakiraman Subramanian : I completely agree with Dr. Owonikoko. Those were very key points and issues that we face as well. In terms of my patients with lung cancer, we haven't had a problem in getting them on clinical trials. Even though we have had carboplatin shortage patients who are already on treatment, they were able to get the carboplatin. For new patients, we were still able to provide them carboplatin as well. The biggest problem for clinical trials has been primarily with my GI colleagues who have to use 5FU. And there, as I said before, we are unable to give bolus 5FU and there is a 10% reduction of the infusional 5FU. So, we can't have any of these patients go on clinical trials. And as a result, anything that has to do with 5FU has come to a screeching halt in terms of clinical trials for our patients. And I think I echo the point of Dr. Owonikoko that by no means this is the last drug shortage we're going to be dealing with and we are here today discussing this, also because this shortage has not ended. It's been ongoing. It's one of the longest drug shortages in my memory as a medical oncologist, and that's concerning. We still see that there is some improvement, but we haven't gotten past it yet. And therefore, as we develop clinical trials and we need to have methods to address drug shortages and how we manage patient enrollment as well as how do we manage existing patients who are already on a clinical trial and, if possible, what might be their options in that situation. We may not have all the answers, but it is definitely an issue that we need to think about in the future as we develop and implement newer clinical trials for our patients. Dr. Vamsi Velcheti: I completely agree and great points, both of you. And we've had the same issues with clinical trials at NYU Langone as well due to the shortage. It's been a challenge, and I think this is a problem that's so complex because of supply chain issues and the way the drugs are priced and incentives for manufacturing these drugs in the United States are not lucrative enough to actually onshore a lot of the production of these drugs. I think at the end of the day, I think we have to come up with some creative, innovative, reimbursement structures for these generic chemotherapy drugs. I think this would require a very complex economic solution that perhaps ASCO and other organizations should kind of really foster an environment of innovation to kind of help facilitate onshoring some of the manufacturing of these key drugs within the United States. I think ASCO is already trying to do that, trying to collaborate with all the stakeholders to kind of address this problem is very critical, and I think all of us have to be engaged in some of the advocacy efforts that are ongoing to kind of address these drug shortages. And this is not a short-term problem. So, Dr. Owonikoko and Dr. Subramanian, any final thoughts before we wrap up the podcast today? Dr. Janakiraman Subramanian: So, Vamsi, you mentioned the whole complex supply chain and the fact that we rely primarily on overseas manufacturers to get these drugs that are off-patent but still a key backbone of our cancer treatment. I think those are all key issues that policymakers and leaders in the field have to keep in mind. As an institution at Inova, one of the key mechanisms that have helped us to sort of stay ahead of the shortage was to have this inventory management team that monitors the inventory out there. And in fact, the inventory management team does have access to what the inventory is in some of their main suppliers in terms of the drugs. And they also have an idea of how many patients are going through treatment, what is the weekly usage of a specific drug like carboplatin. And they try to forecast what is coming down the road and try to prepare for it. And as we try to look for solutions, maybe a forecasting mechanism in a larger scale like either spearheaded by ASCO or by policymakers level that can, for the overall country, try to see where some of the inventory is for some of these critical drugs and try to prepare for it ahead of time, rather than wait till we hit the shortage and then try to find alternative suppliers to get the drug, which obviously doesn't happen quick enough. It takes months or even longer to catch up and get the inventory back to the level where we can comfortably take care of our patients. I think that is something we should be advocating for that as well as the professional societies should take a handle on that and see if they can support something like that as well as letting the institutions know ahead of time what's coming might be very helpful. Dr. Vamsi Velcheti: Yeah, very good point, Janakiraman, and I think that's a key takeaway here. I think we have to learn from other industries and try to– I mean this is not unique to healthcare by any means. I mean these chronic shortages due to supply chain issues, inventory management, there might be some learnings from other industries here that we probably should also focus on inventory management and improve supply chain logistics. Dr. Owonikoko, any closing thoughts? Dr. Taofeek Owonikoko: Yeah, I agree as well with all the points made by Dr. Subramanian and yourself. This is a chronic problem that requires a long-term strategy. I think it's both an economic problem as well as a regulatory problem. As we all know, part of the reason why we went through this current crisis is the regulatory decision by the FDA regarding safety of one of the manufacturers. So being proactive in terms of how these audits are conducted and giving people lead time I think will help avoid similar situations in the future. It's an economic problem. There's a reason why a lot of the big pharma companies are not producing these drugs. And if the cost of production is such that the amount of money you get paid is enough to cover your price, I think there is an economic issue there to be addressed. That is unfortunately not within the scope of what any one of us can do individually, but as advocates in terms of the structure of incentivizing new drug versus old drug, some of these newer drugs are quite expensive, but oftentimes they are used along with standard drugs that are not as expensive. So, where do we strike that balance where we do not stifle innovation but at the same time, we don't create a perverse incentive system where everybody just wants to come up with the newest, most expensive drug and nobody is interested in really producing the backbone chemotherapy and other agents that will make those new drugs work well. So, I think we have to pay attention. We have to advocate for our patients through our different institutions and organizations, and I hope that society as a whole that we've learned a lot of lessons from this crisis and that will help us craft some long-term strategies. Dr. Vamsi Velcheti: Thank you both Dr. Owonikoko and Dr. Subramanian for your time today to speak with me and our listeners and for sharing your insights with us on the ASCO Daily News podcast. Dr. Taofeek Owonikoko: Thank you. Dr. Janakiraman Subramanian: Thank you. Dr. Vamsi Velcheti: And thank you to our listeners for your time today. If you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you so much. 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. ASCO Resources Related to Drug Shortages are available here. Follow today's speakers: Dr. Vamsidhar Velcheti @VamsiVelcheti Dr. Janakiraman Subramanian @RamSubraMD Dr. Taofeek Owonikoko @teekayowo Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Vamsidhar Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Janakiraman Subramanian: Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Daichi, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology, Lilly, Blueprint Medicines, Axcess, BeiGene, Cardinal Health, Takeda, OncoCyte Speakers' Bureau: AstraZeneca, Boehringer Ingelheim, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology Research Funding (Inst.): G1 Therapeutics, Tesaro/GSK, Novartis, Genentech, Novocure, Merck Dr. Taofeek Owonikoko: Stocks and Other Ownership Interests: Cambium Oncology, GenCart, Coherus Biosciences Consulting or Advisory Role: Novartis, Celgene, Abbvie, Eisai, GI Therapeutics, Takeda, Bristol-Myers Squibb, MedImmune, BerGenBio, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Xcovery, Bayer, Merck, Jazz Pharmaceuticals, Zentalis, Wells Fargo, Ipsen, Roche/Genentech, Janssen, Exelixis, BeiGene, Triptych Health Partners, Daichi, Coherus Biosciences Speakers Bureau: Abbvie Research Funding (Inst.): Novartis, Astellas Pharma, Bayer, Regeneron, AstraZenece/MedImmune, Abbvie, G1Therapeutics, Bristol-Myers Squibb, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck, Oncorus, Ispen, GlaxoSmithKline, Calithera Biosciences, Eisai, WindMIL, Turning Point Therapeutics, Roche/Genentech, Mersana, Meryx, Boehringer Ingelheim Patents, Royalties, Other Intellectual Property (Inst.): Overcoming Acquired Resistance to Chemotherapy Treatments Through Suppression of STAT3 Selective Chemotherapy Treatments and Diagnostic Methods Related Thereto DR4 Modulation and Its Implications in EGFR-Target Cancer Therapy Ref: 18089 PROV (CSP) United States Patent Application No. 62/670,210 June 26, 2018 (Co-Inventor) Soluble FAS ligand as a biomarker of recurrence in thyroid cancer; provisional patent 61/727,519 (Inventor) Other Relationship: Roche/Genentech, EMD Serono, Novartis Uncompensated Relationships: Reflexion Medical
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