The US Food and Drug Administration is investigating potential secondary cancer risks associated with CAR T-cell therapy

The US Food and Drug Administration is investigating potential secondary cancer risks associated with CAR T-cell therapy

The US Food and Drug Administration is investigating potential secondary cancer risks associated with CAR T-cell therapy

According to the FDA, there have been reports of T-cell malignancies, including CAR-positive lymphoma, in patients who previously underwent CD19- or BCMA-directed autologous T-cell therapies. These reports are based on postmarketing adverse event (AE) data sources as well as clinical trials.1

The US Food and Drug Administration (FDA) has determined that the risk of T-cell malignancy is evident in all currently approved CD19- and BCMA-based genetically modified autologous T-cell immunotherapies, including:

  • Idecabtagene vicleucel (Abecma), which is indicated for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of treatment, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anticancer . – CD38 monoclonal antibody.2
  • Lisocabtagene maraleucel (Breyanzi), which is indicated for the treatment of adult patients with large B-cell lymphoma (LBCL) who have disease refractory to front-line chemo-immunotherapy or who have relapsed within 12 months of front-line chemo-immunotherapy; Disease refractory to frontline chemoimmunotherapy or who has relapsed after frontline chemoimmunotherapy and is ineligible for hematopoietic stem cell transplantation due to age or comorbidities; Or refractory disease or relapse after at least two lines of systemic therapy.3
  • Ciltacabtagene autoleucel (Carvykti), which is indicated for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, including IMiD, PI, and an anti-CD38 monoclonal antibody.4
  • Tisagenlecleucel (Kymriah), which is indicated for the treatment of patients 25 years of age or younger with precursors of refractory B-cell acute lymphoblastic leukemia (ALL) or in the event of a second or subsequent relapse; Adult patients with relapsed/refractory LBCL who have received at least two prior lines of systemic therapy, excluding those with primary CNS lymphoma; and adult patients with relapsed/refractory follicular lymphoma who have received at least two prior lines of systemic therapy.5
  • Brexucabtagene autoleucel (Tecartus), which is indicated for the treatment of adult patients with relapsed/refractory mantle cell lymphoma and adult patients with relapsed/refractory B-cell precursor ALL.6
  • Axicabtagene ciloleucel (Yescarta), which is indicated for the treatment of adult patients with LBCL refractory to front-line chemoimmunotherapy or who have relapsed within 12 months of front-line chemoimmunotherapy, as well as adult patients with relapsed/refractory LBCL who They received at least 2 prior lines of systemic therapy.7

The FDA emphasizes that although the benefits of these products for their specific uses still outweigh their potential risks, it is investigating the specific risks of malignant T-cell cancer, which may have serious outcomes, such as hospitalization and death.1 The Agency is evaluating whether regulatory action related to these risks is necessary.

All gene therapy products containing integrated lentiviral or retroviral vectors, including CD19- and BCMA-directed genetically modified autologous T-cell immunotherapies, are labeled with a US prescribing information category warning for the development of secondary malignancies. The initial FDA approvals for these products included a postmarketing requirement under Section 505(o) of the Federal Food, Drug, and Cosmetic Act for investigators to conduct 15-year safety observational studies for the purpose of evaluating long-term safety profiles. of these products and the risk of developing secondary malignancies after treatment.

Patients treated with these CD19- and BCMA-directed genetically modified autologous T-cell immunotherapies should receive lifelong monitoring for the development of new malignancies. If a patient develops a new malignant tumor after receiving treatment with these products, he or she should contact the manufacturer of the product in question to report the incident and receive instructions regarding the collection of patient samples that will be tested for the presence of the CAR gene.

Suspected cases, including T-cell malignancies, associated with these products may be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Healthcare providers, clinical researchers, caregivers, and patients with questions about these products may contact FDA’s Center for Biologics Evaluation and Research at ocod@fda.hhs.gov.

References

  1. The US Food and Drug Administration is investigating a serious risk of T-cell malignancies after BCMA-directed or CD19-directed T-cell immunotherapy. New release. Food and Drug Administration. November 28, 2023. Accessed November 29, 2023. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following- bcma -directed-or-cd19-directed-autologous
  2. Your father. Description of information. Bristol-Myers Squibb; 2021. Accessed November 29, 2023. https://packageinserts.bms.com/pi/pi_abecma.pdf
  3. Brianze. Description of information. Bristol-Myers Squibb; 2022. Accessed November 29, 2023. https://www.fda.gov/media/145711/download
  4. Carfacty. Description of information. Janssen Biotechnology; 2023. Accessed November 29, 2023. https://www.fda.gov/media/156560/download
  5. Kymeria. Description of information. Novartis. 2022. Accessed November 29, 2023. https://www.fda.gov/media/107296/download
  6. Ticartos. Description of information. Gilead. 2021. Accessed November 29, 2023. https://www.fda.gov/media/140409/download?attachment
  7. Yescarta. Description of information. Gilead. 2022. Accessed November 29, 2023. https://www.fda.gov/media/108377/download

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