Second Primary Malignancy in Patients with DLBCL Receiving CAR T Therapy and Other Systemic Anticancer Therapy:...

Chimeric antigen receptor T-cell (CAR T) therapy has been linked with second primary malignancies (SPMs) in lymphoma treatment. However, real-world evidence assessing SPM risk in relation to conventional therapies remains limited.

This study compared the risk of SPM between patients receiving CAR T therapy and other systemic anticancer therapy (SACT) for diffuse large B-cell lymphoma.

Adult patients who received either treatment as a second or later line of therapy (LoT) were identified from Komodo Health claims data (October 18, 2017-January 31, 2024). Inverse probability of treatment weighted incidence rates and cumulative incidences of SPM were estimated. The primary outcomes were any SPM, any hematologic SPM, and any solid SPM. Other specific outcomes included SPM by tumor type, covering cell of origin (B cell or T cell) for hematologic SPMs and specific types of SPM.

The study evaluated 1079 CAR T therapy and 4582 SACT LoTs, with a median follow-up of 10.6 months (interquartile range: 4.3-24.3). Risk at 36 months was similar in the CAR T therapy group vs the SACT group for any SPM (37.2% vs 38.5%; P_{0-36 months} = .06) and solid SPM (14.7% vs 17.2%; P_{0-36 months} = .09) and for hematologic SPM (27.4% vs 27.3%; P_{0-36 months} = .13). Lower risk for T-cell malignancies (2.6% vs 4.9%; P_{0-36 months} = .01) and Hodgkin lymphoma (5.4% vs 7.7%; P_{0-36 months} = .02), and higher risk for breast cancer (1.6% vs 0.6%; P_{0-36 months} = .03) and myelodysplastic syndrome (7.1% vs 4.8%; P_{0-36 months} = .05), was observed in the CAR T therapy group.

This study found no evidence of an increased risk of any, solid, or hematologic SPMs overall in CAR T-treated patients in the short term.