Retrospective cohort study of impact of immunotherapy on incidence of second primary malignancies

Immunotherapy (IT) is widely used across multiple cancer types, yet its impact on second primary cancers (SPCs) remains poorly understood. A retrospective cohort study of adult cancer patients treated between 2010 and 2022 across Cleveland Clinic Ohio centers investigated this impact. The study included 5,576 patients with cancer eligible for first-line IT. Among these patients, 1,296 (23%) received first-line IT and 948 (17%) received subsequent-line IT, predoninantly anti-LD-(L)-1 and/or anti-CTLA-4 agents (99.9%). Over a median follow-up of 47.5 months (IQR 27.4-75.4), 264 SPCs were diagnosed. Two- and four-year SPC-free probabilities were 97% and 94%, respectively, in the first-line IT group versus 95% and 92%, respectively, in the non-IT group (p<0.01). In multivariable analysis, IT was associated with a lower hazard of SPC (HR 0.57; p<0.001). The authors conclude that treatment of primary cancer with IT was associated with a reduced clinical incidence of SPCs.