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April 24, 2026Open Access

Treatment-Related Myelodysplastic Syndrome and Acute Myeloid Leukemia Associated with CAR T-Cell Therapies: A Real-World FAERS Pharmacovigilance Study

Key Points

This research aims to assess the long-term risks of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) associated with CAR T-cell therapies.
Analyzed adverse event reports from FAERS spanning January 2013 to February 2025.
Focused on specific CAR T products linked to MDS and AML using reporting odds ratios (RORs).
Conducted subgroup analyses by antigen target.
303 cases of MDS and 129 cases of AML were linked to CAR T therapies.
Notable RORs for brexucabtagene autoleucel (MDS) and axicabtagene ciloleucel (both MDS and AML) indicate significant reporting.
Signals for toxicity were consistent across CD19- and BCMA-directed CAR T agents.

Abstract

Introduction: Chimeric antigen receptor (CAR) T-cell therapies have revolutionized treatment for relapsed/refractory hematologic malignancies, targeting CD19 in B-cell neoplasms and BCMA in multiple myeloma, with response rates exceeding 80%. However, long-term risks, including therapy-related myeloid neoplasms, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are emerging 6–24 months post infusion, potentially linked to lymphodepleting chemotherapy, clonal hematopoiesis expansion, and inflammatory milieus. This FAERS pharmacovigilance analysis quantified MDS/AML reporting across seven FDA-approved CAR-T products to detect antigen-specific signals unattainable in pivotal trials with limited follow-up. Methods: Adverse event reports from FAERS (1 January 2013–10 February 2025) were queried for tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, obecabtagene autoleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel, focusing on MedDRA terms for MDS/AML. Duplicates and ambiguous cases were excluded. Disproportionality was assessed using reporting odds ratios (RORs; lower 95% CI >1 signaling significance), comparing CAR-T-event pairs to database background, with subgroup analyses by antigen target. Results: Among 14,093,557 reports, CAR-T products linked to 303 MDS (brexucabtagene autoleucel ROR 97.93 72.18–132.87, n = 44; axicabtagene ciloleucel ROR 58.70 50.34–68.44, n = 172) and 129 AML cases (axicabtagene ciloleucel ROR 22.89 18.23–28.73, n = 76). Signals were consistent across CD19- and BCMA-directed agents, absent only for recently approved obecabtagene autoleucel. Conclusions: CAR-T therapies exhibit disproportionate MDS/AML reporting in FAERS, supporting class-wide late hematologic toxicity in pretreated patients with clonal hematopoiesis. Enhanced surveillance, baseline profiling, and marrow evaluation for cytopenias are warranted, balancing curative benefits.

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