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Deep Insights Into Big Issues in Myeloma / Research and Treatment at the Sylvester Cancer Center
Deep Insights Into Big Issues in Myeloma / Research and Treatment at the Sylvester Cancer Center image
May 21, 2022 / 09:00AM - 03:30PM EDT
HealthTree Round Tables for Multiple Myeloma Chapter

Event Description

Myeloma Round Table Morning Session: Deep Insights Into Big Issues in Myeloma (Part 1)

Myeloma research and treatment is currently as robust as it has ever been.  Discoveries are being translated into the clinic so quickly that it is hard for physicians and patients to make sense of possible options.  This session features three of the top minds in myeloma today taking deep looks into fundamental issues patients must consider to understand their options.  Weather prevented Dr. Gareth Morgan from appearing live and disrupted the original planned order of the Miami Myeloma Round Table in Aventura, FL on May 21, 2022, but we put it right again on this page.

Dr. Gareth Morgan opens the program with an overview of progress in myeloma.  Dr. Elisabet Manasanch, one of the world leading experts on MGUS and smoldering myeloma, provides an overview for those interested in precursor conditions.  Dr. Nina Shah provides an overview of CAR T and where the therapy is heading in treatment in her last presentation to patients before joining a pharmaceutical firm to start up a myeloma research division.

Gareth Morgan, MD, PhD, New York University, Perlmutter Cancer Center, New York, NY: Multiple Myeloma - Current Status and Future Directions

  • Approximately 33,000 new myeloma diagnosis in U.S. per year
    • 1-2% of all cancers and more common in elderly
    • More common in African Americans
    • Not inherited!
  • Myeloma in family of diseases known as plasma cell dycrasias
    • Myeloma lives in the bone marrow, with other cells that play different roles
    • Myeloma cells = cancerous plasma cells
  • Myeloma cells are abnormal, why they are called clonal
  • Paraprotein or M spike:
    • Can be measured in the blood or urine, protein can either be IgG, IgA, IgD plus kappa or lambda
    • When protein found in urine, called Bence-Jones
    • Tissue damage is consequence of accumulation of M spike, which can lead to:
      • Bone disease: lytic lesions (holes), bone pain, fractures
      • Kidney disease: decrease in urine volume, vomiting, drowsiness or thirst: Remember to drink fluids!
    • Bone marrow suppression
    • Frequent infections
    • High calcium
    • Low hemoglobin (anemia)
  • Genetics
    • Damaged genetic code (DNA) leads to cancerous cells created by abnormal chromosomes
    • Chromosomes come in 23 pairs, plus X or Y, which define gender
    • In myeloma, chromosomes can be either added (gains or amplifications), lost (deletions), or exchanged with one another (translocations, rearrangements).
  • Myeloma biology: what drives plasma cells to produce aberrant proteins (M spikes)
  • Clonal evolution: myeloma cells evolve, changing all the time, cells have different behavior patterns, some die, some mutate, and some hide or diversify
  • Future treatment paradigm:
    • Treat before progression, into complete remission as long as possible.
    • Four agents (drugs) need to be used to maximize response rates and depth of response
  • Immunotherapy: using your own body to cure cancer
    • Drugs improve immune function and tumor killing, reducing multiple myeloma cell burden
    • Immunotherapy attempts to activate T cells to become “angry” enough to see cancer cells and kill them

Elisabet Manasanch, MD, MD Anderson Cancer Center, Houston, TX: Myeloma Precursor Conditions

    • MGUS (monoclonal gammopathy of undetermined significance)
      • M protein <3 g/dL
      • Bone marrow plasma cells <10%
      • No symptoms
      • Low risk of progression to myeloma (1% per year)
      • Low levels of myeloma protein in blood/urine and in bone marrow
    • SMM (smoldering multiple myeloma)
      • M protein >3 g/dL (urine >500 mg)
      • Bone marrow plasma cells 10-60% plasma cells
      • No symptoms
      • Stage between MGUS & myeloma
      • Risk of progression is much larger, there are many ways to measure risk
      • Clinic follow-up every few 2-3 months
    • SMM risk of progression:
      • Intermediate risk: at least 50% at 5 years of diagnosis
      • High-risk: as high as 70% at 2 years of diagnosis
    • Studies accruing about treating SMM with targeted therapy (CD38 Antibodies)

Nina Shah, MD, University of California at San Francisco: Is CAR T Cell Therapy the Answer or an Option?

  • CAR T clinical trials demonstrate progression-free survival and overall survival numbers have been improving
  • How does CAR T differ from other therapies?
    • It is a living drug
    • Quality of life improved as compared to other therapies
  • Practical considerations:
    • Patient eligibility limited to those with more than 4 lines of therapy and no significant co-morbidities
    • Logistics: cell infusion has to be done at specialty center, with co-monitoring between your local MD
  • Some side effects:
    • Cytokine release syndrome (CRS) is a systemic inflammatory response that occurs as CAR T cells activate; can occur 1-14 days after infusion with fever and flu-like symptoms
      • Can progress to life-threatening hypotension and hypoxia
    • Immune effector cell-associated neurotoxicity syndrome (ICAHNS) is a neurotoxicity; causes confusion
      • Important to check the patient’s neurologic state; even handwriting can change
    • Cytopenias
    • Macrophage activation-like syndrome: a systemic inflammatory syndrome

Audience Questions & Answers (Part 1)

Dr. Ola Landgren took the place of Dr. Morgan in this session.

Discussion moderated by Jenny Ahlstrom:

  • 0:20 - What are the factors of innovation in myeloma? How do you develop more disruption?
  • 11:17 - Can we talk about MRD and using it as a new clinical trial endpoint and what that means to patients?
  • 19:20 You talked a lot about CART therapy, and we have new therapies as well (like bispecifics).  How do you choose between all of them?

Audience-submitted questions:

  • 27:30: Cell therapy was once a dream. What do you think we are going to see in the future?
  • 29:30 - I have a lot of questions for my family. My siblings, my children. What should I tell them? Should they get testing done?
  • 35:11 - On the topic of CAR T, I read that there is a clinical trial where manufacturing for CAR T takes only 1 to 2 days. Is that going to make a huge difference?
  • 37:48 - Is durability of CAR T dependent on genotype?  With a CAR-T therapy, where does vaccine therapy come into play with that?
  • 43:43 - I agree that using MRD to decide treatment is an unknown, I'm wondering if whether watching trending is a better indicator?
  • 46:09 - Talking about vaccines, I was offered to get Evusheld. What’s your take of this in myeloma patients?
  • 48:23 - What do you say to patients who are getting at or near remission who nevertheless fear that for the rest of their lives they’ll be in the same kind of treatment? (If you reach complete response do you have to be in therapy forever?)

Myeloma Round Table Afternoon Session: Research and Treatment at the Sylvester Cancer Center (Part 2)

When Dr. C. Ola Landgren moved from New York’s Memorial Sloan Kettering Cancer Center to the University of Miami’s Sylvester Cancer Center, it wasn’t because of the weather.  He has an ambition to create a myeloma research and treatment center of excellence that is second to none.  In this, the second half of the original planned order of the Miami Myeloma Round Table in Aventura, FL on May 21, 2022, Dr. Landgren explains the guiding ideas of the growing myeloma agenda at Sylvester and Dr. Dickran Kazandjian, who was recruited from the National Cancer Institute, explains some of the protocols and treatment strategies in the clinic.

Dr. Elisabet Manasanch joined Drs. Landgren and Kazandjian for the Moderated Discussion/Question & Answer session.

C. Ola Landgren, MD, PhD, University of Miami, Sylvester Cancer Center, Miami, FL: Building a World Class Myeloma Program

    • Our group made several discoveries, publishing more than 50 papers for diverse journals
    • Established an international multiple myeloma research network
    • Have grown about 30% in the past year, doubled our number of patients in one year
    • Enrollment in clinical trials is up, patients are willing to look for options beyond the standard of care, access greater support
    • Labs are working on genomics, assisting data
      • Studying disease through detailed computer models.
    • Biology-driven trials may be the future of research
    • Minimal residual disease (MRD) detection must be refined
      • Can help find the “Achilles heel” for myeloma by characterizing cells
    • FISH and cytogenetics need to move forward
      • “Myeloma-defining genomic events” essential to understand myeloma

Dickran Kazandijan, MD, University of Miami, Sylvester Cancer Center, Miami, FL: Translating Ideas Into Treatment

    • When patients are first diagnosed with myeloma:
      • Physicians usually start treatment with combination treatments for 6-10 cycles (months)
      • Follow up with transplant or stay in maintenance
      • This is always decided between physician and patient
    • Triplets (three drug combinations) for relapsed/refractory myeloma impact progression-free survival (PFS) and overall survival (OS)
      • Myeloma generally takes longer to return, every clinical scenario is different, decision must be made with specialist.
    • What happens after triplet therapies?
      • Assess minimal residual disease status (MRD), studies indicate patients do better
      • Anti-CD38 monoclonal antibodies have revolutionized treatment
      • Quadruplet therapies are new era
    • Quadruplets (four drug combinations)
      • Patients had better response rates
      • Velcade + Revlimid + dexamethasone (VRd) + daratumumab is the most studied
        • MRD negativity rate achieved in 71% of patients!
        • Median time to this was 6 cycles with sustained response
    • What about transplant?
      • Stem cell transplant revolutionized treatment at the end of the 20th century
      • With the introduction of novel therapies in the early 21st century, has seemingly become more questionable
      • But it is still very good option, especially when toxicity from chemo is considered
    • Patients who are not fit for transplant receive VRd+Dara
    • Relapsed/refractory myeloma:
      • More drugs available, many can and should be individualized.
      • CAR T therapy has shown excellent results (Abecma and Carvikti)
      • Sylvester offers several studies with novel immunotherapies
        • Very likely a trial for you

Audience Questions & Answers (Part 2)

Dr. Elisabet Manasanch participated in this session.

Discussion moderated by Jenny Ahlstrom:

  • 0:20 - How do you use all the imaging techniques available (bone marrow biopsy, PET scan, bloodwork) to diagnose myeloma and at relapse?
  • 12:33 - What are the best therapies that you're seeing now for newly diagnosed high-risk disease?  Relapsed/refractory high-risk disease?

Audience-submitted questions:

  • 26:52 - For patients who have been doing well with Revlimid + daratumumab, how worried should we be about the disease coming back and decrease in blood counts?
  • 31:21 - Are we getting any closer to CRISPR being used for myeloma?  What is CRISPR?
  • 32:41 - If a patient did not achieve MRD negativity after SCT (stem cell transplant) or after consolidation, should that patient change treatment?
  • 35:47 - Would you recommend CART for a patient with extramedullary disease?
  • 38:58 - I’m excited about the slide Jenny alluded to about comparative PETs. Is this the most sensitive scan is available to all myeloma patients or just in a trial?
  • 42:17 -  Is it recommended that low-risk or stable smoldering multiple myeloma patients retrieve their cells for ASCT (autologous stem cell transplant)?

 

Thanks to our Round Table sponsors

           

Schedule & Agenda

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Welcome & Introduction
09:00AM
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Most Important Questions for Patients & Researchers
09:10AM
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Progression: From Precursors to Myeloma
09:30AM
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Is CAR T the Answer or an Option?
09:50AM
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Behind the Scenes of HealthTree Cure Hub
10:10AM
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Break
10:25AM
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Faculty discussion
10:40AM
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Round Table Audience Q&A – Drs. Manasanch, Morgan and Shah
11:05AM
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Lunch
11:45AM
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Ola Landgren – Myeloma at Sylvester: Ambition for Results
12:45PM
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Myeloma at Sylvester: Ambition for Results
12:45PM
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Translating Ideas into Treatment
01:05PM
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Nurses: (Pro)Active & Essential Partners
01:25PM
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Break
01:45PM
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Faculty discussion
02:00PM
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Round Table Audience Q&A – Drs. Landgren, Kazandjian and Mr. Verducci
02:25PM

Speakers & Moderators

The panelist C. Ola Landgren, MD, PhD
C. Ola Landgren, MD, PhD

C. Ola Landgren, MD, PhD, is Professor of Medicine, Chief of the Myeloma Program, and Leader of the Experimental Program at the University of Miami Sylvester Cancer Center. Read more about his move to Miami here. Dr. Landgren is a pioneer in the drug development and minimal residual disease (MRD) testing in myeloma. In collaboration with colleagues throughout the world, he develops new strategies (including cell-based, molecular-based, and imaging-based) and continues to be a leader of using advanced MRD testing in clinical trials. He is involved in the service’s rational treatment program (small molecule, monoclonal antibody, immune-based) for newly diagnosed, relapsed and refractory myeloma and amyloidosis patients. His research focuses on early drug development, advanced disease monitoring by new minimal residual disease (MRD) assays and biomarkers, and immune-PET to monitor treatment. He also studies mechanism and markers of progression from MGUS/smoldering myeloma to symptomatic multiple myeloma, and the identification of high-risk precursor patients who may be candidates for early treatment. Prior to joining Miami, Dr. Landgren was the Chief Attending Physician of the Myeloma Service at Memorial Sloan Kettering and Professor of Medicine at the Weill Cornell Medical College in New York City and Chief of the Multiple Myeloma Section of the National Cancer Institute in Bethesda, MD. Dr. Landgren received his MD at Karolinska Institute in Stockholm, Sweden; and he has had fellowships at Karolinska University Hospital and the National Cancer Institute. He is a frequent speaker at national and international meetings, and has published more than 400 peer-reviewed papers.

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The panelist Nina Shah, MD
Nina Shah, MD

Dr. Nina Shah is a specialist in blood diseases who focuses on treating multiple myeloma, a type of cancer affecting certain cells in the bone marrow. Her areas of professional interest include the intersection of immunology and oncology as well as helping patients fight multiple myeloma by boosting their immune systems. Shah earned a bachelor's degree in cognitive neuroscience at Harvard University, followed by a medical degree from New York University School of Medicine. She completed a residency in internal medicine at Columbia University and a fellowship in hematology-oncology at the University of Texas MD Anderson Cancer Center. Shah belongs to the American Society of Clinical Oncology, American Society of Hematology and American Society for Transplantation and Cellular Therapy. She speaks Bengali and Spanish.

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The panelist Dickran Kazandjian, MD
Dickran Kazandjian, MD

Dr. Kazandjian’s clinical and translational research interests lie in the treatment of precursor plasma cell disorders including high risk smoldering multiple myeloma and the role of immunotherapy in plasma cell dyscrasias. In addition, he is re-evaluating the role of autologous stem cell transplant (ASCT) in the era of highly efficacious novel-novel drugs, immunotherapy biologics, and cell-based therapies with the hypothesis that certain subsets of patients with myeloma may not benefit by default upfront ASCT.

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The panelist Elisabet Manasanch, MD
Elisabet Manasanch, MD

Dr. Manasanch specializes in the treatment of patients with multiple myeloma. Furthermore, she focuses on translational research of the precursor stages of myeloma and early disease management through groundbreaking immunotherapy-focused clinical trials.

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The panelist Gareth Morgan, MD, PhD
Gareth Morgan, MD, PhD

Gareth Morgan, MD, PhD, is Director of Multiple Myeloma Research at NYU Langone Perlmutter Cancer Center in New York, NY. He is an internationally recognized clinician-scientist in the molecular genetics of blood cell cancers and myeloma treatment. He has a particular focus on diagnostic prevention and treatment strategies for high-risk and relapsed/refractory myeloma. Dr. Morgan is doing influential work on the characterization of the myeloma genome, defining specific subsets of the disease that have prognostic importance, and developing personalized therapeutic strategies targeted to each subtype. He is also engaged in advanced research in molecular diagnostics, drug development, and clinical trials. His research aims to cure myeloma and to reduce side effects by targeting treatment to the biology underlying each patient’s cancer. Prior to leading the Perlmutter Cancer Center’s myeloma program, Dr. Morgan was Professor of Medicine and Director of the Myeloma Institute at the University of Arkansas for Medical Sciences and Professor of Hematology and Director of the Centre for Myeloma Research at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research in London, Europe’s largest comprehensive cancer institute. He is also a founding director of the European Myeloma Network and has authored more than 500 peer-reviewed journals. Dr. Morgan received his doctorate on the genetics of leukemia from the University of London in 1991 and his bachelor of medicine in 1981 from the Welsh National School of Medicine. His post graduate medical training was completed in Wales and at the Royal Postgraduate Medical School in London.

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The panelist Dennis Verducci MSN, RN, NP-BC, OCN
Dennis Verducci MSN, RN, NP-BC, OCN

Dennis has vast experience with multiple myeloma after treating patients in various capacities, such as on the bone marrow transplant unit and outpatient teams of prestigious centers such as Hackensack, John Theurer, and Memorial Sloan-Kettering Cancer Center (MSK). He now is working as a Nurse Practitioner at the University of Miami alongside renowned myeloma specialist, Dr. Ola Landgren.

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