FDA Approves Cilta-cel to Treat R/R Multiple Myeloma

FDA approval is based on CARTITUDE-1, a phase 1b/2 trial in which investigators reported that cilta-cel produced an objective response rate (ORR) of 98% and a stringent complete response rate of 78%.

The list of approved chimeric antigen receptor (CAR) T-cell therapies grew by 1 Monday as Janssen and Legend Biotech’s ciltacabtagene autoleucel (cilta-cel) received approval for treatment of relapsed or refractory multiple myeloma.

The BCMA-directed immunotherapy, to be sold as Carvykti, will be the second such therapy for multiple myeloma, following approval of idecabtagene vicleucel (ide-cel), nearly a year ago. However, Abecma, sold by Bristol Myers Squibb, has been beset by manufacturing problems since its launch, leaving room for competition.

Multiple myeloma is a cancer that affects white blood cells in the bone marrow. Although many therapies have been developed to treat it, the disease is incurable. The likelihood of disease progression rises once patients have received treatments from the 3 major therapy classes—immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Under the FDA approval, patients must receive at least 4 treatments, including 1 in each of these classes, before being considered for cilta-cel.

FDA approval is based on CARTITUDE-1, a phase 1b/2 trial in which investigators reported that cilta-cel produced an objective response rate of 98% (95% CI, 92.7%-99.7%) and a stringent complete response rate of 78% (95% CI, 68.8%-86.1%). Median duration of response was 21.8 months after a median of 18 months of follow-up.

Recent data presented at the 2021 American Society of Hematology meeting in Atlanta, Georgia, found that 74% of patients were alive at 2 years, with progression free survival at 61%.

"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," principal study investigator Sundar Jagannath, MD, director of the Center of Excellence for Multiple Myeloma and professor of medicine, hematology, and medical oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, said in a statement. "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."

Janssen officials said in their statement that cilta-cel will be offered in a limited network at first, to allow for the proper training and certification of oncologists who will administer the personalized therapy. Availability of the treatment will increase throughout 2022 and beyond, the statement said.

“This approval of Janssen's first cell therapy is a testament to our continuing commitment in oncology to deliver new therapeutic options and drive toward our vision of the elimination of cancer," said Mathai Mammen, MD, PhD, executive vice president, Pharmaceuticals, Janssen Research & Development, LLC, Johnson & Johnson. "Today's approval underscores our determination to develop therapies that can help patients living with what remains an intractable blood cancer today and at the same time offer hope for the future."