The U.S. Food and Drug Administration has approved labeling changes for Johnson & Johnson and Legend Biotech's CAR-T cell therapy Carvykti (ciltacabtagene autoleucel) to include a boxed warning for a potentially fatal gastrointestinal condition. The regulatory action follows reports of immune effector cell-associated enterocolitis (IEC-EC) in patients treated with the blood cancer therapy.
Serious Gastrointestinal Safety Signal Emerges
The FDA received reports of IEC-EC from both clinical trials and postmarketing adverse event data. This serious gut inflammation condition has led to life-threatening complications including bowel perforation and sepsis in some patients. IEC-EC is a form of inflammation of the intestines triggered by the immune system that was observed weeks to months after CAR-T therapy treatment with Carvykti.
Patients with IEC-EC presented with severe or prolonged diarrhea, abdominal pain, and weight loss requiring total parenteral nutrition. Treatment required various immunosuppressive therapies including corticosteroids, in addition to supportive care. The condition was associated with fatal outcomes from gut perforation and sepsis.
Updated Clinical Management Guidelines
The FDA has updated the boxed warning, warnings and precautions, and adverse reactions sections of Carvykti's prescribing information and medication guide to include the risk of IEC-EC. Patients and clinical trial participants with IEC-EC should be managed according to institutional guidelines including referral to gastroenterology and infectious disease specialists.
In patients with treatment refractory IEC-EC, additional work up should be considered to rule out T cell lymphoma of the gastrointestinal tract, which has been reported in patients with treatment refractory IEC-EC in the postmarketing setting.
Survival Benefits Support Continued Use
Despite the new safety concerns, the FDA determined that Carvykti's overall benefits continue to outweigh the potential risks for its approved use. The agency also updated the clinical studies section of the drug's prescribing information to include overall survival data from the CARTITUDE-4 trial.
The interim data from the late-stage study showed a statistically significant improvement in survival for patients receiving Carvykti compared to those on standard therapy, with a median follow-up of 33.6 months. This randomized, open-label, multicenter controlled study evaluated adult patients with relapsed and lenalidomide-refractory multiple myeloma who previously received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.
Treatment Context and Approval History
Carvykti was first approved in February 2022 and received expanded approval in April 2024 for adults with relapsed or refractory multiple myeloma who had received at least one prior line of therapy. Multiple myeloma is an incurable blood cancer that affects plasma cells, a type of white blood cell found in the bone marrow.
The FDA emphasized that continuous monitoring and assessment of the safety of all biologics, including Carvykti, remains a priority and the agency remains committed to informing the public when new safety information becomes available about these products.
