The FDA has adjusted the label of Johnson & Johnson and Legend Biotech’s Carvykti, warning patients and doctors that use of the multiple myeloma treatment could increase the risk of an intestinal inflammatory disorder, which can be fatal.
The FDA’s boxed warning is for immune effector cell-associated enterocolitis (IEC-EC). The condition has developed in some patients within weeks or months after infusion of the CAR-T cell therapy, leading to diarrhea, abdominal pain and weight loss, according to the FDA. The disorder can be fatal when it causes gut perforation and sepsis.
The warning comes after reports of IEC-EC from clinical trials and post-marketing adverse event data, the FDA said. Those who have developed IEC-EC have been treated with immunosuppressive therapies, including corticosteroids, and with nutritional bloodstream infusions, which bypass the digestive system.
In its safety communication, the U.S. regulator added that the benefit of Carvykti “continues to outweigh the potential risks” of the treatment.
Based on a retrospective analysis of clinical trials, IEC-EC has occurred in 1% of those who have received Carvykti, a J&J spokesperson said.
“We are committed to supporting patients who receive Carvykti, understanding how patients respond to therapy, and ensuring health care professionals have the most updated safety information and management considerations,” the J&J spokesperson added.
More than 8,500 patients have been treated with Carvykti, and the drug has demonstrated significant progression-free survival and overall survival benefits, J&J's spokesperson said. In patients receiving one to three prior lines of therapy and through nearly three years of follow-up, Carvykti has reduced the risk of death by 45% over standard therapies.
The FDA recommends that patients with IEC-EC should be referred to gastroenterology and infectious disease specialists. Those with refractory IEC-EC should additionally be screened for T-cell lymphoma of the gastrointestinal tract, as it has been reported in some patients in the post-marketing setting, the regulator said.
Last year, the FDA added a boxed warning to all CAR-T treatments for the risk of secondary T-cell cancers. The other blood cancer CAR-T drugs on the market are Novartis’ Kymriah, Bristol Myers Squibb’s Breyanzi and Abecma and Gilead’s duo of Tecartus and Yescarta.
Four months ago, the FDA removed its Risk Evaluation and Mitigation Strategies (REMS) requirements for CAR-T blood cancer drugs, which were in place because of the risk of cytokine release syndrome and neurological toxicities associated with the drugs. Under the REMS program, hospitals and clinics had to be specially certified to administer CAR-T therapies.
The FDA approved Carvykti in 2022 and expanded its use to as early as the second-line setting last year. With sales of $808 million in the first half of this year, Carvykti has surpassed Yescarta as the world’s top-selling CAR-T. Yescarta, which became the first CAR-T blockbuster in 2022, generated sales of $779 million in the first half of this year.