FDA Postpones Decision on Cilta-Cel for Relapsed/Refractory Multiple Myeloma


The PDUFA date for Cilta-Cel has been moved in order to evaluate new data and is now set for early 2022.

The Prescription Drug User Fee target data for the chimeric antigen receptor (CAR) T cell therapy ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) for the treatment of adult patients with relapsed and/or refractory multiple myeloma has been extended to February 28, 2022, according to a press release by the Legend Biotech Corporation.1

Cilta-cel is a CAR T-cell therapy that is designed to be used for the treatment of relapsed and/or refractory multiple myeloma in the earlier lines of treatment. It is made up of a structurally differentiated CAR T with 2 BCMA-targeting single domain antibodies.

The extension was made to allow for sufficient time to review information submitted pertaining to an updated analytical method that was made following an FDA information request. The application is supported by the phase 1/2 CARTITUDE-1 study (NCT03548207), which has an estimated enrollment of 126 participants and an estimated study completion date of August 11, 2022. Primary end points of the study include the number of participants with adverse events (AEs) and objective response rate (ORR). Secondary end points include 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.2

During the single-arm study, all patients received a single infusion of the experimental therapy after lymphodepletion.

At the data cutoff of September 1, 2020, 97 patients with a median of 6 prior lines of therapy receive cilta-cel. The ORR was 97% (95% CI, 91%-99%) with 67% of patients achieving a stringent complete response. The median time to first response was 1 month with a median time to complete response or better of 2 months (range, 1-15). Overall, 57 patients were evaluated for minimal residual disease (MRD), and 93% were MRD-negative. At 12 months, the PFS was 77% and the OS was 89%. Median PFS was not reached. 3

In terms of safety, Grade 3/4 hematologic AEs included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Cytokine release syndrome (CRS) occurred in 95% of patients with a median duration of 4 days. Grade 3/4 CRS occurred at a rate of 4%. CAR T neurotoxicity occurred in 21% of patients. Fourteen deaths occurred over the course of the study, 5 of which were due to disease progression and 4 due to treatment-related AEs.

In order to participate in the study, patients must have received at least 3 prior lines of treatment, have documented disease progression, measurable disease, and an ECOG performance status of o or 1. Patients who have received previous CAR T therapy, heart failure, myocardial infraction, have received an allogenic stem cell transplant within 6 months before apheresis, or known active or a history of central nervous system involvement are not eligible to participate.

“We are working closely with Janssen and the FDA to facilitate an efficient and thorough review of the BLA for cilta-cel,” said Ying Huang, PhD, chief executive officer and chief financial officer at Legend Biotech, in a press release. “We remain confident that cilta-cel has shown great promise in patients with relapsed and refractory multiple myeloma, and we are focused on making this therapy available to them in the United States as soon as possible.”

1.Legend Biotech announces extension of PDUFA date for Cilta-Cel. News release. Legend Biotech. November 1, 2021. Accessed November 2, 2021. https://bit.ly/3CFU4U6
2.A Study of JNJ-68284528, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). ClinicalTrials.gov. Accessed November 2, 2021. https://bit.ly/3EHZPRR
3.Usmani S, Berdeja J, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. J Clin Oncol. 2021;39(15):8005. doi: 10.1200/JCO.2021.39.15_suppl.8005
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