FDA Flags New Safety Risk for Carvykti: Immune Effector Cell Associated Enterocolitis Added as Boxed Warning in Label

The U.S. Food and Drug Administration (FDA) has issued a boxed warning, a strongest form of safety alert, for Carvykti (Ciltacabtagene Autoleucel)  a CAR-T cell therapy marketed by Johnson & Johnson and Legend Biotech after identifying cases of a severe gastrointestinal complication known as immune effector cell-associated enterocolitis (IEC-EC) among treated multiple myeloma patients.​

About Warning

The FDA received reports from both clinical studies and post-marketing surveillance indicating that certain patients developed IEC-EC weeks to months after Carvykti infusion. The condition presents with symptoms such as severe diarrhea, abdominal pain, and significant weight loss, occasionally requiring parenteral nutrition. In some cases, the intestinal inflammation led to bowel perforation and sepsis, resulting in fatal outcomes.​

In addition to IEC-EC and gastrointestinal perforation, the FDA’s supplemental approval letter for Carvykti also highlights the risk of gastrointestinal T-cell lymphoma as a serious adverse event, reported in post marketing surveillance. Patients presenting with persistent or severe gastrointestinal symptoms after Carvykti treatment should be thoroughly evaluated to rule out this rare but critical complication. Biopsy and specialist consultation are recommended to differentiate between IEC-EC and T-cell lymphoma of the gastrointestinal tract, as timely diagnosis is essential for appropriate management and to prevent fatal outcomes.

The warning now forms part of the official Boxed Warning, Warnings and Precautions, and Post-marketing Adverse Reactions sections in Carvykti prescribing information and medication guide.​

Clinical Benefit: Survival Advantage Confirmed

Despite the safety warning, the FDA underscored that Carvykti benefit-risk profile remains favorable, citing long-term overall survival (OS) gains observed in the CARTITUDE-4 trial, a pivotal, randomized phase 3 study in lenalidomide-refractory multiple myeloma patients. After a median follow-up of 33.6 months, Carvykti demonstrated a statistically significant improvement in OS compared to standard therapy, confirming its critical role in advanced myeloma management.​

 Understanding Immune Effector Cell-Associated Enterocolitis (IEC-EC)

IEC-EC is an immune-mediated inflammatory reaction in the gastrointestinal tract that can mimic severe inflammatory bowel disease. The disorder may lead to lasting GI dysfunction and, without timely intervention, cause fatal complications.​

The FDA explained that IEC-EC cases typically respond to a combination of supportive care (IV fluids, TPN) and immunosuppressive therapy such as corticosteroids. For treatment-refractory cases, specialists may use targeted biologic agents (e.g., infliximab or vedolizumab) and conduct biopsies to exclude gastrointestinal T-cell lymphoma, which has emerged in rare post-marketing cases.​

FDA Approval History and Initial Safety Profile

Carvykti (Ciltacabtagene Autoleucel) received FDA approval in March 2022 as the first BCMA-targeted CAR-T cell therapy for adults with relapsed or refractory multiple myeloma who had undergone at least one prior line of therapy, including a proteasome inhibitor and immunomodulatory agent. The approval was based on robust efficacy data demonstrating significant response rates and durable remissions in heavily pretreated patients. Initially, Carvykti’s safety profile included well-characterized risks typical of CAR-T therapies such as cytokine release syndrome and neurotoxicity; however, gastrointestinal toxicities like immune effector cell-associated enterocolitis (IEC-EC) were not prominent in early clinical data. Post-marketing surveillance began to reveal IEC-EC as a serious delayed adverse event.

Prescribing Guidance and Monitoring Recommendations

Healthcare professionals are advised to:

Monitor for delayed GI symptoms such as diarrhea and weight loss for several months post-infusion.

Consult gastroenterology and infectious disease specialists upon first suspicion of IEC-EC.

Report adverse events related to IEC-EC through FDA Med Watch for continual pharmacovigilance.​

This update also strengthens existing Risk Evaluation and Mitigation Strategy (REMS) requirements for all CAR-T therapies.

Regulatory Context and Future Monitoring

The FDA continues to prioritize the ongoing safety monitoring of CAR-T therapies like Carvykti. Agency will keep carefully reviewing new safety data and may update Carvykti labeling further if new side effects or risks are identified in the future. Current data supports continued clinical use, provided that prescribers follow gastrointestinal monitoring protocols and manage adverse responses promptly.​