Dr. Cohen on Mitigation Strategies for CAR T-Cell Therapy in Multiple Myeloma

Adam D. Cohen, MD, assistant professor of medicine, director, Myeloma Immunotherapy, University of Pennsylvania, discusses mitigation strategies that can be used for patients with relapsed/refractory multiple myeloma who are receiving the CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel).

The phase 1/2 CARTITUDE-1 study (NCT03548207) examined cilta-cel in patients who had received 3 or more prior lines of therapy or were double refractory to a proteasome inhibitor and an immunomodulatory drug (IMiD) and had received a proteasome inhibitor, IMiD, and an anti-CD38 antibodty.

Results from an analysis of the trial showed that these patients had a least 2 of the following features: high tumor burden, grade 2 or higher cytokine release syndrome (CRS), prior immune effector cell–associated neurotoxicity syndrome (ICANS), as well as very high CAR T-cell expansion and persistence, according to Cohen. These findings inspired mitigation strategies that were incorporated in the studies that followed CARTITUDE-1, Cohen explains. 

One strategy was to allow investigators to give their choice of bridging therapy to reduce the risk of rapid progression during manufacturing, Cohen notes. In CARTITUDE-1, patients were restricted to receive the same therapies they had previously received. As such, many patients were highly refractory and progressed through manufacturing and bridging therapy, according to Cohen.

Additional efforts include more aggressive management of CRS and ICANS, a handwriting analysis for all patients because micrographia was an early sign of movement and neurocognitive-like disorders, and prolonged neurologic monitoring beyond the first 100 days of treatment, Cohen explains. The incidence of neurocognitive and movement disorders has decreased dramatically since these efforts were implemented, Cohen concludes.