On February 28, 2022, the FDA approved ciltacabtagene autoleucel (Carvykti; Janssen Biotech) for the treatment of adults with relapsed or refractory multiple myeloma after ≥4 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. Ciltacabtagene autoleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. It is the second BCMA-directed CAR T-cell therapy approved by the FDA for this patient population. The FDA granted this application a priority review, a breakthrough therapy designation, and an orphan drug designation.
The FDA approval of this new CAR T-cell therapy was based on results of the CARTITUDE-1 clinical trial, an open-label, phase 1/2 multicenter study of 97 patients with relapsed or refractory multiple myeloma who received ≥3 previous lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody, whose disease progressed during or after the last chemotherapy regimen; 82% of the patients had received ≥4 lines of antimyeloma therapy.
“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,” said Sundar Jagannath, MD, Director, Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine, Mount Sinai, and principal study investigator. “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 overall response rate (ORR) and the duration of response (DOR) with ciltacabtagene autoleucel were evaluated using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. The ORR was 97.9% (95% confidence interval [CI], 92.7-99.7). Among the 95 patients who had a response to the CAR T-cell therapy, the median DOR was 21.8 months (95% CI, 21.8-not evaluable), with a median duration of follow-up of 18 months.
The drug’s prescribing information includes a boxed warning for cytokine-release syndrome (CRS), hemophagocytic lymphohistiocytosis or macrophage activation syndrome, immune effector cell–associated neurotoxicity syndrome, Parkinson disease, Guillain-Barré syndrome, and prolonged and/or recurrent cytopenia, all of which are life-threatening.
The most common adverse reactions with ciltacabtagene autoleucel were pyrexia, CRS, hypogammaglobulinemia, musculoskeletal pain, fatigue, infections, diarrhea, nausea, encephalopathy, headache, coagulopathy, constipation, and vomiting.
Ciltacabtagene autoleucel is approved with a Risk Evaluation and Mitigation Strategy program requiring that providers who administer this medication must be certified to recognize and manage CRS and neurologic adverse events. The FDA is requiring the manufacturer to conduct a postmarketing study to verify the safety of the drug in patients who received ciltacabtagene autoleucel.