FDA Approves Cilta-Cel for Relapsed/Refractory Multiple Myeloma


Ciltacabtagene autoleucel had been granted FDA approval for the treatment of select patients with relapsed or refractory multiple myeloma.

The FDA has granted approval of ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of adults with relapsed or refractory multiple myeloma who have received 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, according to an announcement by Legend Biotech Corporation.1

Review of the approval application for cilta-cel, a chimeric antigen receptor (CAR) T-cell therapy with 2 B-cell maturation antigen (BCMA)-targeting single domain antibodies, was expected to be completed in 2021, but the FDA extended the review period to allow for sufficient time to review information submitted about an updated analytical method that was made following an FDA information request.

Approval was granted based on data from the phase 1/2 CARITUDE clinical trial (NCT03548207), in which cilta-cel administered as a single infusion at a dose range of 0.5 to 1.0 x 106 CAR-positive viable T cells per kg of body weight achieved an overall response rate (ORR) of 98% (95% CI, 92.7%-99.7%), and a stringent complete response rate of 78% (95% CI, 68.8%-86.1%). Responses to the CAR T cells were deep and durable. At a median follow-up of 18 months, the median duration of response was 21.8 months (95% CI, 21.8 to not estimable).2

“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse with fewer patients achieving a deep response as they progress through later lines of therapy,” said principal study investigator Sundar Jagannath, MD, MBBS, professor of medicine, hematology and medical oncology at Mount Sinai, in a press release.1 “This is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population. Today’s approval of Carvykti helps address a great unmet need for these patients.”

CARITUDE investigated 97 patients with relapsed/refractory multiple myeloma with an open-label, single arm, multi-center design. The phase 1 coprimary end points were the percentage of patients with adverse events (AEs) and the percentage with severe AEs. The phase 2 primary end point was ORR. As secondary end points, the investigators looked at levels of BCMA expressing cells and soluble BCMA, systemic cytokine concentrations, levels of CAR-T cells, duration of response, progression-free survival (PFS), overall survival (OS), time to response, health related quality of life, and change from baseline health-related quality of life.1,2

Two-year follow-up results from the study were presented recently at the American Society of Hematology Annual Meeting. In terms of efficacy, the analysis showed that the median time to first response was 1 month with a median time to complete response or better of 2 months (range, 1-15). Fifty-seven patients were evaluated for minimal residual disease (MRD), and 91.8% were MRD-negative. At the 18-month timepoint, the PFS rate was 66.0% (95% CI, 54.9%–75.0%) and the OS rate was 80.9% (95% CI, 71.4%–87.6%). In the population of patients with sustained MRD for more than 6 months and more than 12 months, the PFS rate was 96.3% and the OS rate was 100%. The median PFS was not reached.2

Grade 3/4 hematologic AEs were observed and included neutropenia (94.8%), anemia (68.0%), leukopenia (60.8%), thrombocytopenia (59.8%), and lymphopenia (49.5%). Cytokine release syndrome was reported in 94.8% of patients but were predominantly grade 1 and 2.

The FDA-approved label for cilta-cel mentions the common grade 3/4 AEs along with Guillain-Barré syndrome, peripheral neuropathy, cranial nerve palsies, and hemophagocytic lymphohistiocytosis.1

Prior to its approval for the treatment of patients with relapsed or refractory multiple myeloma who have received 4 or more prior lines of therapy, cilta-cel was granted breakthrough designation and orphan drug designation by the FDA. Applications for approval under this indication have also been filed for cilta-cel in Europe.


1. Carvykti™ (ciltacabtagene autoleucel), BCMA-directed car-t therapy, receives u.s. fda approval for the treatment of adult patients with relapsed or refractory multiple myeloma. News release. February 28, 2022. Accessed February 28, 2022. https://bit.ly/3str0w9

2. Martin T, Usmani SZ, Berdeja JG, et al. 549 Updated results from CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor t cell therapy, in patients with relapsed/refractory multiple myeloma. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, Georgia. Abstract 549.

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