The Food and Drug Administration (FDA) has approved Carvykti (ciltacabtagene autoleucel) for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) after 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Carvykti is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Upon binding BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

The approval was based on data from the open-label, single-arm, phase 1b/2 CARTITUDE-1 study (ClinicalTrials.gov Identifier: NCT03548207), which evaluated the efficacy and safety of ciltacabtagene autoleucel in adults with RRMM who had disease progression after receiving a median of 6 prior treatment regimens (range, 3-18), and had previously received a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The primary endpoint was overall response rate (ORR).

Based on a median duration of follow-up of 18 months, results showed an ORR of 97.9% (95% CI, 92.7-99.7) among 97 efficacy-evaluable patients, with 78.4% (95% CI, 68.8-86.1) achieving a stringent complete response, 16.5% (95% CI, 9.7-25.4) achieving very good partial response, and 3.1% (95% CI, 0.6-8.8) achieving partial response. The median duration of response was 21.8 months (95% CI, 21.8–not estimable) and the median time to first response was 1 month (range, 0.9 to 10.7 months).

“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 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. “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.”

Updated results from CARTITUDE-1 presented at the American Society of Hematology 2021 Annual Meeting showed an ORR of 98% at the 22-month follow-up, with 83% of patients achieving a stringent complete response.

As for safety, the most common nonlaboratory adverse reactions were pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. 

Carvykti carries a Boxed Warning for cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome and prolonged and recurrent cytopenia, all of which can be life-threatening. The product is available only through a restricted program called the Carvykti REMS Program.

Carvykti is provided as a single dose for infusion containing a suspension of CAR-positive viable T cells in 1 infusion bag. In a press release, the Company stated that the therapy would initially be provided through a limited network of certified treatment centers, with an expected increase in availability through 2022.

References

  1. US 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. The Janssen Pharmaceutical Companies of Johnson & Johnson. February 28, 2022. Accessed March 1, 2022. https://www.prnewswire.com/news-releases/us-fda-approves-carvykti-ciltacabtagene-autoleucel-janssens-first-cell-therapy-a-bcma-directed-car-t-immunotherapy-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma-301492211.html
  2. Carvykti. Package insert. Janssen Biotech, Inc.; 2022. Accessed March 1, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf