On February 28, 2022, the FDA approved Carvykti (ciltacabtagene autoleucel; from Janssen Biotech) for the treatment of adults with relapsed (coming back) or refractory (not responding to therapy) multiple myeloma after 4 or more lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. Carvykti is a BCMA-directed genetically modified autologous CAR T-cell therapy, also known as gene therapy. It is the second BCMA-directed CAR T-cell therapy approved by the FDA for this patient population.
The FDA approval was based on results of the CARTITUDE-1 clinical trial, an open-label, phase 1/2 multicenter study that included 97 patients with relapsed or refractory multiple myeloma who received 3 or more previous lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody, whose cancer progressed during or after the last chemotherapy regimen.
“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, New York, and principal study investigator.
“The approval of cilta-cel [Carvykti] provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” Dr. Jagannath added.
The overall response rate and the duration of response with Carvykti were evaluated using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Of the 97 patients in the study, almost all—95 patients (or 97.9%)—had a response to the new CAR T-cell therapy. Among the 95 patients who had a response to Carvykti, the average duration of response was 21.8 months.
The most common adverse reactions with Carvykti were fever, cytokine-release syndrome, hypogammaglobulinemia, musculoskeletal pain, fatigue, infections, diarrhea, nausea, encephalopathy, headache, coagulopathy, constipation, and vomiting.
Like all CAR T-cell therapies, Carvykti is associated with potentially serious or life-threatening side effects, including cytokine-release syndrome, hemophagocytic lymphohistiocytosis or macrophage-activation syndrome, immune-related neurologic side effects, Parkinson disease, Guillain-Barré syndrome, and recurrent cytopenia.
For this reason, Carvykti is approved with a Risk Evaluation and Mitigation Strategy program requiring providers who administer this drug to be certified in the management of these serious side effects.
