There have been reports of T-cell malignancies among patients who have undergone CD19- or BCMA-directed autologous CAR T-cell immunotherapies.
FDA Is Investigating Potential Secondary Cancer Risks Associated CAR T-Cell Therapy
According to the FDA, there have been reports of T-cell malignancies, including CAR-positive lymphoma, developing in patients who had previously undergone CD19- or BCMA-directed autologous CAR T-cell therapies. These reports are based on postmarketing adverse event (AE) data sources as well as clinical trials.1
The FDA has determined that the risk of T-cell malignancies is apparent in all currently approved CD19- and BCMA-directed genetically modified autologous CAR T-cell immunotherapies, including:
The FDA emphasizes that although the benefits of these products in their indicated uses continue to outweigh their potential risks, it is investigating the identified risk of T-cell malignancy, which may have serious outcomes, such as hospitalization and death.1 The agency is evaluating whether regulatory action pertaining to this risk is necessary.
All gene therapy products with integrating lentiviral or retroviral vectors, including CD19- and BCMA-directed genetically modified autologous T-cell immunotherapies, are labeled with a United States prescribing information class warning for the development of secondary malignancies. The initial FDA approvals of these products included postmarketing requirements per Section 505(o) of the Federal Food, Drug, and Cosmetic Act for investigators to conduct 15-year observational follow-up safety studies for the purpose of assessing the long-term safety profiles of these products and the risk of developing secondary malignancies after treatment.
Patients being treated with these CD19- and BCMA-directed genetically modified autologous T-cell immunotherapies should receive life-long monitoring for the development of new malignancies. If a patient develops a new malignancy after receiving treatment with these products, they should contact the respective product’s manufacturer to report the incident and receive instructions regarding the collection of patient samples that will be tested for the presence of the CAR transgene.
Suspected AEs, including T-cell malignancies, related to these products can be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Health care providers, clinical investigators, caregivers, and patients with questions about these products can contact the FDA’s Center for Biologics Evaluation and Research at ocod@fda.hhs.gov.
References
Shared Model of Care Post-HCT Offers Safe Follow-Up, Reduces Patient Burden
Published: March 19th 2025 | Updated: March 19th 2025Alternating post-HCT care between specialized facilities and local cancer centers produced noninferior non-relapse mortality and similar quality of life to usual care.