Cilta-Cel Earns FDA Priority Review for Relapsed/Refractory Multiple Myeloma


Based on data from the CARTITUDE-1, the BCMA-targeting CAR T-cell therapy ciltacabtagene autoleucel moves forward towards regulatory approval in multiple myeloma.

The biologics license application for ciltacabtagene autoleucel (cilta-cel) for the treatment of patients with relapsed or refractory multiple myeloma has been accepted and granted priority review by the FDA, announced Legend Biotech Company, who is responsible for developing the chimeric antigen receptor (CAR) T-cell therapy.1

Data supporting the application are from the phase 1b/2 trial CARTITUDE-1 (NCT03548207), in which the B-cell maturation antigen (BCMA) therapy is being examined for safety and efficacy in the indicated patient population.

“Cilta-cel has shown great promise in the treatment of patients with heavily pretreated multiple myeloma according to study findings reported to date. Today’s priority review designation marks another significant milestone for this cell therapy,” Ying Huang, PhD, CEO and CFO of Legend Biotech, said in a press release. “We look forward to our continued collaborative efforts with Janssen and in working with the FDA to bring this transformative therapy to patients who are in need of new treatment options.”

Results of the trial were previously presented at the 2020 American Society of Hematology Annual Meeting & Exposition. Patients had progressive multiple myeloma per International Myeloma Working Group criteria with either experience on at least 3 prior therapies—including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy—or double refractory disease. Participants needed an ECOG performance status of 0 or 1.2

If necessary, patients were treated with bridging therapy followed by lymphodepleting chemotherapy of cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m2 on days –5 to –3. The CAR T-cell therapy target dose was 0.75 x 106 viable CAR-positive T cells/kg.

Primary end points for phase 1b were safety and finding the recommended phase 2 dose. In phase 2, the primary outcome measure was objective response rate (ORR).

There was a 96.9% ORR, with 67.0% of patients achieving a stringent complete response (sCR), 25.8% with a very good partial response, and 4.1% with a partial response; 72.2% of responses were ongoing at the data cutoff. The median time to first response was 1 month (range, 0.9-8.5).

Minimal residual disease (MRD) negativity (10-5) occurred in 93.0% of evaluable patients (n = 57), with a median time to MRD negativity of 1 month (range, 0.8-7.7). Thirty-three patients (34.0%) had both sCR and MRD negativity.

Median progression-free survival (PFS) was not reached in responders. The rate of PFS at 12 months was 76.6% (95% CI, 66.0%-84.3%). In those with an sCR and partial response, those rates were 84.5% (95% CI, 72.0%-91.8%) and 68.0% (95% CI, 46.1%-82.5%), respectively.

Cytokine release syndrome, a common CAR T-cell therapy–related adverse effects, was reported in 94.8% of patients at any grade but only 4.1% of those were grade 3/4 in severity.

Cilta-cel is a second-generation CAR T-cell therapy consisting of a CD3ζ signaling domain, a 4-1BB costimulatory domain, and 2 BCMA binding domains. Previously, cilta-cel was granted fast track designation by the FDA for the treatment of patients with relapsed or refractory multiple myeloma.3 The Prescription Drug User Fee Act (PDUFA) target action date for this application is November 29, 2021.


1. U.S. Food and Drug Administration Grants BCMA CAR-T Cilta-cel Priority Review for the Treatment for Relapsed/Refractory Multiple Myeloma. News release. Janssen. December 6, 2019. Accessed May 27, 2021.

2. Madduri D, Berdeja JG, Usmani SZ, et al. 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. Presented at: 2020 ASH Annual Meeting and Exposition; December 5-8, 2020; Virtual. Abstract 177.

3. Janssen Announces BCMA CAR-T Therapy JNJ-4528 Granted U.S. FDA Breakthrough TherapyDesignation for the Treatment of Relapsed or Refractory Multiple Myeloma. News release. Janssen. December 6, 2019. Accessed May 27, 2021.

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