Adam Cohen, MD, discusses when patients should receive chimeric antigen receptor T-cell therapies for relapsed/refractory multiple myeloma.
Adam Cohen, MD, director of myeloma immunotherapy at Penn Medicine and associate professor of medicine at the Hospital of the University of Pennsylvania, discusses when patients should receive chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory multiple myeloma (R/R MM).
Two B-cell maturation antigen (BCMA)-targeted CAR T-cell therapies have been approved for R/R MM: ciltacabtaene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma). Patients must have received 4 prior lines of therapy including a proteasome inhibitor, immunomodulatory drug (IMiD), and anti-CD38 antibody. Cohen says that older patients can be treated as long as they have good performance status, but severe cardiac and pulmonary conditions may cause patients to not be candidates for CAR T-cell therapy. However, those with renal failure may be treated successfully by modifying the level of lymphodepleting chemotherapy received.
Cohen recommends that patients be referred for CAR T-cell therapy when they progress on third-line therapy and move on to fourth-line therapy, since there may be long wait times to receive these therapies. They can then receive CAR T cells if they fail to have a strong response to fourth-line therapy. Referring patients early is crucial due to the time it takes to manufacture CAR T cells, since patients who progress rapidly may not live long enough to benefit from CAR T-cell therapy even with bridging therapy.
0:08 | Right now, both BCMA CAR [T-cell] products in myeloma are approved for patients who have had at least 4 prior lines of therapy, which must include a proteasome inhibitor, IMiD, and a CD38 antibody. There's no real upper age limit for CAR T-cell therapy. We've treated patients in their early 80s, but they do need to be fairly robust to be able to withstand cytokine release syndrome. Typically, we would exclude patients with advanced heart failure or uncontrolled cardiac conditions, oxygen independence, COPD [chronic obstructive pulmonary disease], or other severe pulmonary conditions or very poor performance status. We don't think renal failure necessarily is an exclusion. They were excluded from the trials, but we have been able to treat patients with commercial products even with profound renal dysfunction, just modifying the lymphodepleting chemotherapy.
0:56 | I think the time to think about sending your patient into the CAR T-cell center should be when they're progressing on their third-line therapy and you're thinking about starting a fourth-line treatment. Then it would be helpful if you're thinking there would be a CAR T-cell candidate to get them into the center so we can assess them at the same time and add them to the waitlist for CAR T cells. Unfortunately, there's still limited manufacturing slots for these, so there can be a several month waitlist. That way, that patient is already in the system and if they don't respond to fourth-line treatment, or even if they are responding well but it's not a deep response, we may be able to take them to CAR T cells while they're under good disease control.
1:33 | We're learning that patients who are really progressing rapidly while we're trying to collect T cells and then manage them with bridging therapy during the manufacturing [process] has been challenging. Some of those patients unfortunately never make it to their CAR T cells because their disease just takes off. I think it's better to send them in while they're still under some control and while we have good bridging options.