Anti-BCMA CAR T-Cell Therapy May Extend PFS in Patients with Refractory Multiple Myeloma

Ciltacabtagene autoleucel (Carvykti), a chimeric antigen receptor (CAR) T-cell therapy, may extend progression-free survival (PFS) in patients with lenalidomide-refractory multiple myeloma (MM) compared with physician’s choice of standard care.

Risk of disease progression or death was cut by nearly three-quarters (74%) with ciltacabtagene autoleucel compared with standard care, according to the results of a phase III randomized, open-label trial published in the New England Journal of Medicine.

“The strong progression-free survival benefit and rapid and deep response with [ciltacabtagene autoleucel] highlight the potential for [ciltacabtagene autoleucel] to become a therapeutic option for patients with myeloma after the first relapse,” the researchers wrote.

In the CARTITUDE-4 trial, patients with lenalidomide-refractory MM were randomized to receive ciltacabtagene autoleucel or the physician’s choice of effective standard care — pomalidomide/bortezomib/dexamethasone or daratumumab/pomalidomide/dexamethasone. All patients previously received one to three lines of treatment, including a proteasome inhibitor and an immunomodulatory drug. Notably, in the CAR T-cell group, 30 patients (14.4%) had triple-class drug resistance.

The median PFS was not reached in the treatment group and was 11.8 months in the standard-care group at a median follow-up of 15.9 months. At 12 months, PFS was 75.9% with ciltacabtagene autoleucel and 48.6% with the standard-care group. More patients in the CAR T-cell group had an overall response (84.6% versus 67.3%), a complete response or better (73.1% versus 21.8%), and an absence of minimal residual disease (60.6% versus 15.6%) compared with the standard-care group, respectively. Any-cause death was reported for 39 patients and 46 patients, respectively.

In terms of safety, more than three-quarters of patients (76.1%) who received ciltacabtagene autoleucel had cytokine release syndrome, a commonly seen side effect for CAR T-cell therapies. In addition, 4.5% had immune effector cell–associated neurotoxicity syndrome (grade 1/2), 9.1% had cranial nerve palsy (grade 2/3) and 2.8% had CAR-T–related peripheral neuropathy.

Ciltacabtagene autoleucel is a CAR T-cell therapy that targets B cell maturation antigen (BCMA), which is overexpressed on malignant plasma cells. The overexpression and activation of BCMA are associated with the progression of MM cells. The Food and Drug Administration approved the therapy last year to treat adult patients with relapsed/refractory MM after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

Lenalidomide is the recommended treatment for newly diagnosed and relapsed/refractory MM. However, with the widespread use of lenalidomide as early-line treatment, including as maintenance therapy, the frequency of lenalidomide resistance early in treatment has also risen, signaling a need for other treatments.

Janssen and Legend Biotech, which manufacture ciltacabtagene autoleucel, funded the study.