Dr Mohan on AEs Associated With CAR T-cell Therapy in R/R Myeloma

Meera Mohan, MD, MS, FACP, assistant professor, Department of Medicine, Division of Hematology, Medical College of Wisconsin, medical oncologist, Froedtert Hospital, discusses adverse effects (AEs) associated with CAR T-cell therapy in relapsed/refractory multiple myeloma.

Although the emergence of CAR T-cell therapies and bispecific antibodies have provided effective treatment options for heavily pretreated patients with relapsed/refractory multiple myeloma, these treatments are associated with different toxicities vs other agents used in the multiple myeloma space. Steroid-refractory cytokine release syndrome (CRS) and steroid-refractory immune effector cell–associated neurotoxicity (ICANS) are both AEs that could accompany treatment with CAR T-cell therapy, Mohan explains, adding that there is room for improvement in the management of these toxicities.

Moreover, cytopenias are also linked to treatment with CAR T-cell therapy. In the phase 1/2 CARTITUDE-1 trial (NCT03548207), which supported the FDA approval of ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, grade 3 or 4 hematologic toxicities included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Cytopenias negatively affect quality of life for patients and increase health-care burden, Mohan notes.

Hypogammaglobulinemia is an additional AE associated with BCMA-directed CAR T-cell therapy and bispecific antibodies, Mohan continues. This could lead to infections, and intravenous immunoglobulin replacement as a primary prophylaxis could be considered for the management of hypogammaglobulinemia, she adds.

With the emergence of these novel AEs, developing optimal infection monitoring, prophylaxis, and treatment strategies is important in the era of these newer therapies, Mohan concludes.