Second Primary Malignancies after CAR T-Cell Therapy: A Systematic Review and Meta-analysis of 5,517 Lymphoma and Myeloma Patients

作者：Tobias Tix, Mohammad Alhomoud, Roni Shouval, Edward R. Scheffer Cliff, Miguel‐Angel Perales, David M. Cordas dos Santos, Kai Rejeski · 发表于：Clinical Cancer Research · 年份：2024 · DOI：10.1158/1078-0432.ccr-24-1798 · 被引用次数：104 · 研究领域：CAR-T cell therapy research、Multiple and Secondary Primary Cancers、Acute Lymphoblastic Leukemia research

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events, including second primary malignancies (SPM) that impact morbidity and mortality. To delineate the frequency and subtypes of SPMs following CAR-T in lymphoma and myeloma, we performed a systematic review and meta-analysis. EXPERIMENTAL DESIGN: A literature search was conducted in the MEDLINE, Embase, and Cochrane CENTRAL databases. Following the extraction of SPM cases and assignment of malignant origin, we analyzed SPM point estimates using random effects models. RESULTS: We identified 326 SPMs across 5,517 patients from 18 clinical trials and 7 real-world studies. With a median follow-up of 21.7 months, the overall SPM point estimate was 6.0% (95% confidence interval, 4.8%-7.4%). SPM estimates were associated with treatment setting (clinical trials > real-world studies), duration of follow-up, and number of prior treatment lines, which were each confirmed as independent study-level risk factors of SPM in a meta-regression model. A subgroup meta-analysis of the four trials that randomized CAR-T versus standard-of-care revealed a similar risk of SPM with either treatment strategy (P = 0.92). In a distribution analysis of SPM subtypes, hematologic malignancies were the most common entity (37%), followed by solid tumors (27%) and non-melanoma skin cancers (16%). T-cell malignancies represented a small minority of event...