FDA Expands CAR T Approvals for Patients With Multiple Myeloma

The Food and Drug Administration approved additional indications for two chimeric antigen receptor (CAR) T-cell therapies used to treat patients with relapsed or refractory multiple myeloma (MM) last week. The expanded approvals provide new options for earlier treatment of MM.

Ide-Cel (Abecma)

First, FDA expanded approval of idecabtagene vicleucel (ide-cel, Abecma) to treat triple-class exposed adult patients with relapsed or refractory multiple myeloma (MM) after two or more prior lines of therapy. Ide-cel, manufactured by Bristol Myers Squibb and 2seventy bio, Inc., was previously approved after four prior lines of treatment.

FDA expanded the approval based on results from the phase 3 KarMMa-3 trial, which demonstrated a 51% reduction in the risk of disease progression or death compared to standard regimens in patients with relapsed and refractory MM with two to four prior lines of treatment and were refractory to the last treatment regimen. Previous treatments included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. CD38 is expressed on MM cells, making it a good target for immunotherapeutic approaches.

The safety profile of ide-cel was consistent with that observed in previous studies, and the most common adverse events were low-grade cytokine release syndrome (CRS) and neurotoxicity.

Ide-cel includes a boxed warning for CRS, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), prolonged cytopenia and secondary hematological malignancies.

Cilta-Cel (Carvykti)

FDA approved Johnson & Johnson’s ciltacabtagene autoleucel (cilta-cel, Carvykti) to treat adult patients with relapsed or refractory MM who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. The approval makes cilta-cel the first and only B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy approved to treat patients with MM as early as first relapse.

FDA based its approval on results from the phase 3 CARTITUDE-4 study, which demonstrated that the earlier use of cilta-cel reduced the risk of disease progression or death by 59% compared to standard therapies in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.

The safety profile for cilta-cel includes a boxed warning for CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), Parkinsonism and Guillain-Barre syndrome and their associated complications, HLH/MAS, prolonged and recurrent cytopenias and secondary hematological malignancies.