Cilta-Cel Snags FDA Approval for Relapsed/Refractory Multiple Myeloma


Newly FDA-approved ciltacabtagene autoleucel was found to induce an objective response rate of 98% in patients with relapsed/refractory multiple myeloma.

The FDA has approved ciltacabtagene autoleucel (Carvykti; cilta-cel) to treat patients with relapsed/refractory multiple myeloma (RRMM) and have undergone 4 lines of prior therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1

The regulatory decision was supported by data from the CARTITUDE-1 study (NCT03548207), which demonstrated that single treatment with cilta-cel yielded an overall response rate of 98% among patients (n = 97) with RRMM (95% CI, 92.7%-99.7%). Furthermore, among patients who achieved a response, 78% (n = 76) achieved a stringent complete response (sCR). sCR is achieved when a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment.

At an 18-month median follow-up, the median duration of response (DOR) was 21.8 months. Moreover, the 12-month progression-free survival rate was 77% (95% CI, 66.0%-84.3%) and the overall survival (OS) rate was 89% (80.2%-93.5%). Neither the median DOR (95% CI, 15.9-not estimable [NE]) or median progression-free survival were reached (16.8-NE).2

Cilta-cel is a CAR T-cell therapy with 2 B-cell maturation antigen (BCMA)-targeting single domain antibodies. These antibodies are constructed to confer high avidity against human BCMA—which is primarily expressed on malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells. Once the agent has bonded to the BCMA-expressing cells, the CAR ignites T-cell activation, expansion, and the consequent elimination of target cells.

“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” lead study author Sundar Jagannath, MD, Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and principal study investigator, stated in a press release. “The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time.”

The single-arm, open label, phase 1b/2 CARTITUDE-1 trial enrolled 113 patients with RRMM across 16 different institutions in the US. Enrolled participants had received a median of 6 prior treatments (range, 3-18) including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. A total of 97 enrolled patients received a single infusion of cilta-cel at the recommended dose of 0.75 x 106 CAR-positive viable T cells per KG. Treatment was administered 5-7 days after start of lymphodepletion.

Grade 3/4 hematological adverse events (AEs) included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Approximately 95% of patients experienced cytokine release syndrome (CRS), with a median to onset of 7 days and a median duration of 4 days. Except for 1 grade 5 case of CRS, all CRS and hemophagocytic lymphohistiocytosis events resolved. Twenty patients (21%) experienced CAR T-cell neurotoxicity, and 14 patients passed away during the study: 6 deaths were because of treatment-related AES, 5 were because of related to progressive disease, and 3 were because of treatment-unrelated adverse events.

Cilta-cel will only be available under the restricted program known as the CARVYKTI™ Risk Evaluation and Mitigation Strategy (REMS) Program. The agent’s safety information includes boxed warnings regarding cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, parkinsonism and Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged or recurrent cytopenias. Other precautions include recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, and effects on ability to drive and use machines.

“We are committed to harnessing our science, deep disease understanding and capabilities to bring forward cell therapies like Carvykti as we continue to focus on our ultimate goal of delivering a cure for multiple myeloma,” Peter Lebowitz, MD, PhD, global therapeutic area head, oncology, Janssen Research & Development, LLC, which develops cilta-cel with Legend Biotech, stated in a press release. “We extend our sincere gratitude to the patients, their families and the teams of researchers and study centers who have participated in the clinical study of Carvykti and enabled today’s approval.”


  1. U.S. FDA approves CARVYKTI™ (ciltacabtagene autoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed February 28, 2022.
  2. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8
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