FDA Updates Boxed Warning for Cilta-Cel Following Reports of Immune Effector Cell–Associated Enterocolitis

The FDA has announced updated labeling for ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech, Inc.) following reports of immune effector cell–associated enterocolitis (IEC-EC) in patients treated for multiple myeloma (MM).

The decision follows a review of data from both clinical trials and postmarketing adverse event (AE) reports, which indicated cases of IEC-EC occurring within weeks to months after infusion. As a result, the FDA has added this condition to the product’s boxed warning, underscoring the need for early recognition and management of gastrointestinal (GI) symptoms among treated patients.

Cilta-cel is a B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy, initially approved by the FDA in 2022 for adults with relapsed or refractory MM after at least 4 prior lines of therapy. In 2024, the indication was expanded to include patients who had received 1 or more prior lines of treatment, based on data from the pivotal CARTITUDE-1 trial (NCT03548207). In that study, cilta-cel demonstrated an overall response rate (ORR) of approximately 98% and a median duration of response of 21.8 months, marking a major therapeutic advance for heavily pretreated MM populations.^1,2

Despite its remarkable efficacy, cilta-cel has been associated with several serious and potentially fatal toxicities, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), prolonged cytopenias, and secondary hematologic malignancies, including T-cell malignancies. The addition of IEC-EC to the boxed warning further expands the scope of post-treatment monitoring required for this therapy.³

What Is IEC-EC?

IEC-EC is characterized by inflammation of the gastrointestinal tract that can lead to severe or prolonged diarrhea, abdominal pain, and significant weight loss, sometimes necessitating total parenteral nutrition (TPN). According to the FDA, the condition has, in some cases, resulted in gut perforation, sepsis, and death. Management of IEC-EC has typically included supportive care, nutritional support, and immunosuppressive therapy, most commonly corticosteroids.³

The FDA advises that patients exhibiting symptoms consistent with IEC-EC should be promptly evaluated according to institutional guidelines, with early referral to gastroenterology and infectious disease specialists. For those with treatment-refractory IEC-EC, additional diagnostic workup is recommended to rule out T-cell lymphoma of the gastrointestinal tract, which has been reported in postmarketing settings.³

Despite the newly identified risks, the agency emphasized that the overall benefit-risk profile of cilta-cel remains favorable, noting its demonstrated overall survival benefit in treated patients. “FDA has determined that the overall benefit of Carvykti continues to outweigh the potential risks for the approved use,” the agency stated in its official communication.³

For pharmacists, the label change highlights the importance of monitoring for delayed-onset adverse events in patients who have received CAR T-cell therapy and ensuring timely coordination of care among oncology, gastroenterology, and infectious disease teams. Early identification of IEC-EC symptoms and appropriate management can be critical in mitigating complications and preserving patient outcomes.

REFERENCES

1. Gerlach A. Can cilta-cel redefine outcomes in multiple myeloma? Pharmacy Times. August 6, 2025. Accessed October 13, 2025. https://www.pharmacytimes.com/view/can-cilta-cel-redefine-outcomes-in-multiple-myeloma-

2. A study of JNJ-68284528, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). Updated July 30, 2025. Accessed October 13, 2025. https://www.clinicaltrials.gov/study/NCT03548207#study-overview

3. FDA approves labeling changes that include a boxed warning for immune effector cell-associated enterocolitis following treatment with ciltacabtagene Autoleucel (CARVYKTI, Janssen Biotech, Inc.). FDA. October 10, 2025. Accessed October 13, 2025. https://www.fda.gov/safety/medical-product-safety-information/fda-approves-labeling-changes-include-boxed-warning-immune-effector-cell-associated-enterocolitis