Carvykti Black Box Warning About Gastrointestinal Risks Added By FDA

New warning comes amid ongoing concerns that side effects of the entire class of CAR-T medications could increase the risks of cancer.

The blood cancer treatment Carvykti has been linked to an increased risk of serious and potentially life-threatening gastrointestinal inflammation, according to federal regulators, who have determined the risks require the strongest label warning a medication can carry.

The U.S. Food and Drug Administration (FDA) issued a drug safety communication on October 10, announcing that it is requiring a new Carvykti black box warning after receiving reports of immune effector cell-associated enterocolitis (IEC-EC), a condition that causes inflammation in the colon and small intestines.

The warning indicates that IEC-EC side effects from Carvykti can result in severe or prolonged diarrhea, abdominal pain and weight loss that requires intravenous feeding to address.

The FDA first approved Carvykti (ciltacabtagene autoleucel) for the treatment of multiple myeloma in 2022, indicating it should be used only after doctors have tried four or more prior types of therapy first. It belongs to a class of drugs known as chimeric antigen receptor T-cell therapy (CAR-T), a form of altered gene therapy also approved for use in patients with advanced, difficult-to-treat, or reoccurring lymphoma, leukemia and other blood cancers.

Over the past few years, the entire class has come under closer scrutiny due to adverse side effects, with the FDA requiring several CAR-T medications, including Carvykti, to add black box warnings in January 2024, indicating that the side effects may increase the risk of T-cell malignancies, which can result in hospitalization and death. The decision came after the agency’s researchers found 22 cases of secondary cancer linked to CAR-T side effects.

According to this new Carvykti warning, the FDA recently completed a review of data from clinical trials and postmarketing adverse event reports. It found that some Carvykti IEC-EC cases were linked to patient deaths due to gut perforation and sepsis. The condition reportedly occurred in Carvykti patients weeks to months after their first infusion.

However, the agency believes the benefits of Carvykti still outweigh the risks, so the FDA is requiring IEC-EC updates to the Boxed Warning, Warning and Preparations, and Adverse Reactions – Postmarketing experience sections of the Medication Guide and prescribing information, which is the strongest label warning a manufacturer can be required to place on their drug.

The FDA warning alerts doctors and patients to the potential gastrointestinal risks, and indicates the condition should be treated with supportive care, total parenteral (intravenous) nutrition and treatment with various immunosuppressive therapies, including corticosteroids.

“Patients and clinical trial participants with IEC-EC should be managed according to the 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.”

– FDA Carvykti Drug Safety Communication

The agency indicated it will update the public when more information is available.

CAR-T Therapy Cancer Concerns

The new warning comes amid ongoing concerns about CAR-T cancer risks. In December 2023, less than two years after the drug was released, the FDA linked 22 cases of T-cell cancers to treatment with CAR-T medications, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma and cutaneous T-cell lymphoma. All of these appeared to have manifested within two years of treatment.

As a result of the risks associated with side effects of Carvykti and other CAR-T cell treatments, the FDA recommends that patients or clinical trial participants receiving these treatments be monitored closely in the weeks following treatment, and regularly for the rest of their life by a health care professional for new cancers that may develop.

Some of the cases are still under investigation, but cancer incidents have been reportedly linked to five of the six CAR-T cell drugs on the market, including Abecma, Breyanzi, Carvykti, Kymriah and Yescarta.

The agency warns that the cases are still under investigation, raising concerns that postmarketing reports may underestimate the number of cancer cases caused by the drugs.

The FDA calls for patients who experience Carvykti side effects, including IEC-EC, to contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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