FDA Investigates Risk of T-cell Malignancy Following Chimeric Antigen Receptor (CAR) T cell Immunotherapies
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What is happening?
On Nov. 28, 2023, US FDA announced it is investigating the risk of T-cell malignancies in patients who received autologous Chimeric Antigen Receptor (CAR) T cell immunotherapies and is evaluating the need for regulatory action. FDA also provided methods to report suspected adverse events.
Summary:
FDA has received reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR-T cell immunotherapies. Reports were received from clinical trials and/or postmarketing adverse event (AE) data sources.
FDA has determined that the risk of T-cell malignancies is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR-T cell immunotherapies.
Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action.
Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies.
Background:
Potential risk of developing secondary malignancies is currently labeled as a class warning in the US prescribing information (USPIs) for approved BCMA-directed and CD19-directed genetically modified autologous T cell immunotherapies.
The initial approvals of these products included postmarketing requirements (PMRs) under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA) to conduct 15-year long term follow-up observational safety studies to assess the long-term safety and the risk of secondary malignancies occurring after treatment.
FDA-approved BCMA-directed and CD19-directed CAR-T products include the following:
- BMS’ Abecma (idecabtagene vicleucel)
- BMS’ Breyanzi (lisocabtagene maraleucel)
- Janssen’s Carvykti (ciltacabtagene autoleucel)*
- Novartis’ Kymriah (tisagenlecleucel)
- Kite’s Tecartus (brexucabtagene autoleucel)
- Kite’s Yescarta (axicabtagene ciloleucel)
*See publication link below pertaining to a case of T-cell lymphoma (TCL) derived from CAR-T cells reported in a patient who had received ciltacabtagene autoleucel (cilta-cel).
Gilead/Kite is not aware of any evidence to date that treatment with Yescarta or Tecartus has a causal role in the development of these malignancies of T-cell origin. The potential risk of secondary T-cell lymphoma as a result of CAR T-cell therapy infusion is known and is included in the prescribing information for both Yescarta and Tecartus. Kite’s latest analysis, recently shared with FDA includes more than 13,000 patients treated with Yescarta and more than 2,700 patients treated with Tecartus.
Source:
Link to FDA Announcement
Additional information:
Simon J. et al, CAR+ T-Cell Lymphoma Post Ciltacabtagene Autoleucel Therapy for Relapsed Refractory Multiple Myeloma, Blood, Volume 142, Supplement 1, 2023, Page 6939, ISSN 0006-4971, https://doi.org/10.1182/blood-2023-178806