FDA Extends BLA PDUFA Date for CAR T-Cell Therapy for Multiple Myeloma


Ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy is currently being evaluated for the treatment of patients with relapsed and/or refractory multiple myeloma.

The FDA has granted an extension of the Prescription Drug User Fee Act (PDUFA) date to February 28, 2022, for the Biologics License Application (BLA) filed by Janssen for ciltacabtagene autoleucel (cilta-cel).1

The B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy is currently being evaluated for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM). The FDA granted the extension to the PDUFA date to allow sufficient time to review data recently submitted by Janssen on an updated analytical method for the treatment based on an FDA information request; however, no additional clinical data were requested.1

In the preliminary phase 1b/2 portion of the CARTITUDE-1 study, data showed that a single low-dose infusion of cilta-cel resulted in early, deep, and durable responses in heavily pretreated patients with MM, with a safety profile consistent with that of the prior LEGEND-2 study.2

The CAR T-cell therapy has 2 B-cell maturation antigen—targeting single-domain antibodies designed to confer avidity. A prior LEGEND-2 study conducted in China investigating the LCAR-B38M CAR T-cell therapy demonstrated deep, durable responses with a manageable safety profile in patients with RRMM.

In the CARTITUDE-1 study conducted in the United States, eligible patients aged 18 years or older who were diagnosed with MM based on the International Myeloma Working Group (IMWG) criteria were included for assessment. These eligible patients also needed to have measurable disease, Eastern Cooperative Oncology Group performance status below or equal to 1, received at least 3 or more prior treatment regimens or were double refractory to a proteasome inhibitor and immunomodulatory drug, and were administered an anti-CD38 antibody.

Following apheresis, bridging therapy was possible for patients. Treatment with cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m2 daily for 3 days were used for lymphodepletion. Five to 7 days following the start of lymphodepletion, a single infusion of cilta-cel at the target dose of 0.75×106 in the range between 0.5 and 1.0×106 CAR-positive viable T cells/kg was administered to patients.

In the phase 1b portion of the study, the primary objective was to characterize the safety of cilta-cel. In the phase 2 portion of the study, the primary objective was to evaluate ciltacabtagene autoleucel efficacy, allowing for the establishment of the recommended dose.

By May 20, 2020, 97 patients with RRMM received cilta-cel. The patients included in the analysis were 58.8% male, with a median age 61.0 years. The median follow-up period was 8.8 months (range 1.5—20.4), with patients receiving a median of 6 prior lines of therapy. Of these prior lines of therapy, 83.5% were penta-exposed, 87.6% were triple-refractory, 41.2% were penta-refractory, and 97.9% were refractory to the last line of therapy.2

The overall response rate was found to be 94.8%, with a stringent complete response rate of 55.7%, a very good partial response rate of 32.0%, and partial response rate of 7.2%. Additionally, all of the patients observed achieved a reduction in M-protein.

In December 2020, Janssen announced initiation of a rolling submission of its BLA to the for cilta-cel, which was accepted under FDA Priority Review in May 2021.1


  1. Janssen Announces Extension of U.S. FDA BLA PDUFA Date for BCMA CAR-T Ciltacabtagene Autoleucel. Janssen, November 1, 2021. https://www.jnj.com/janssen-announces-extension-of-u-s-fda-bla-pdufa-date-for-bcma-car-t-ciltacabtagene-autoleucel
  2. Results from CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen—Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma. Poster presented at: ASH 2020 Virtual Conference. December 5, 2020.

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