Myeloma Round Table: Deep Insights Into Big Issues in Myeloma — Miami, May 21, 2022 (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

Questions & Answers

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?)

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