Secondary Malignancies Following CAR T-Cell Therapy for B-Cell Malignancies: A Retrospective Analysis

Chimeric antigen receptor T-cell (CART) therapy has shown clinical efficacy in relapsed and refractory large B-cell malignancies. There is emerging data on the long-term complications including risk of secondary malignancies. We aimed to describe the incidence and characteristics of secondary malignancies following CART therapy.

We performed a single-center retrospective analysis of a prospectively collected cohort of 87 patients who received CART therapy for relapsed/refractory B-cell malignancies between January 2020 and August 2023.

Seven patients (8.0%) developed a secondary malignancy, with a median age of 57 years (40-77) and mean time to onset of 16.9 months (3-34.5 months). Two patients were diagnosed with MDS and five with AML. Six patients had cytogenetic abnormalities at diagnosis of MDS/AML. Five patients received hypomethylating agents and two received an allogeneic stem cell transplant as treatment for their myeloid malignancy. Two patients were alive at 12 months after diagnosis of their myeloid malignancy. The 12-month cumulative incidence function (CIF) was 2.3% (95% CI, 0.4%-7.3%) and the 24-month CIF was 6.9% (95% CI, 2.4%-14.4%).

Development of a secondary malignancy is a potential complication following CART therapy. Results of this single-center study should be confirmed with larger multicenter studies. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.