Systematic literature review of secondary primary malignancies related to a CAR-T treatment in patients with multiple myeloma, lymphoma or leukemia.

BACKGROUND

Chimeric antigen receptor (CAR)-T cell therapies have transformed the treatment landscape of hematologic malignancies. However, concerns have emerged regarding the potential development of secondary primary malignancies (SPMs) in treated patients. This systematic literature review (SLR) evaluated the incidence, and risk factors of SPMs following CAR-T therapy.

METHODS

The SLR was conducted in accordance with PRISMA guidelines. Comprehensive searches were performed in MEDLINE, Embase, the Cochrane Library, and relevant clinical trial registries from inception through October 2024. Eligible studies included patients with lymphoma, multiple myeloma (MM), or leukemia who received CAR-T therapy and reported on SPM outcomes, including occurrence and incidence, time to onset, SPM-related mortality, and associated risk factors or causality.

RESULTS

Of 6737 screened records, 131 studies were included for data synthesis. Median SPM occurrence was 4.5% (IQR: 2.5-8.5%) among 20,014 CAR-T-treated patients, with median incidence of 3.1 per 100 patient-years. Hematologic SPMs accounted for 46% of cases; T-cell malignancies were rare. Median time to onset ranged from 2.0 to 38.4 months. SPM-related mortality was reported in a median of 1.7% (IQR: 0.9-3.6%) of patients. Of 434 cases where cause was discussed, five cases were attributed to CAR-T therapy, while the rest were mainly linked to prior cytotoxic therapies, advanced age, or genetic predisposition.

CONCLUSIONS

The incidence of SPMs following CAR-T therapy is generally modest and varied across studies. Pre-existing risk factors continue to confound attribution of these SPMs to CAR-T therapy. These findings support continued CAR-T use with risk-adapted surveillance strategies.