A new study published in Clinical Cancer Research suggests that CAR T-cell therapy does not increase the risk of developing second primary malignancies (SPMs) compared to standard cancer treatments. The systematic review and meta-analysis, encompassing data from over 5,500 patients with lymphoma and myeloma, offers reassurance regarding the long-term safety of this innovative immunotherapy.
The research team, led by Tobias Tix from LMU Klinikum in Munich, analyzed data from 18 clinical trials and seven real-world studies to determine the frequency and types of SPMs occurring after CAR T-cell therapy. The overall SPM point estimate was 5.8% with a median follow-up of 21.7 months.
Similar SPM Risk Compared to Standard Care
Importantly, a subgroup meta-analysis of four trials that randomized patients to either CAR T-cell therapy or standard of care found no significant difference in SPM risk between the two groups. This suggests that the risk of secondary cancers is not elevated by CAR T-cell treatment itself.
Factors Influencing SPM Development
The study identified several factors that may influence the development of SPMs. These include the treatment setting (clinical trials versus real-world settings), the duration of follow-up, and the number of previous treatment lines a patient had received. Meta-regression analysis confirmed these as independent risk factors at the study level.
Types of Second Primary Malignancies
Among the SPMs identified, hematologic malignancies were the most common (37%), followed by solid tumors (27%) and nonmelanoma skin cancers (16%). T-cell malignancies were rare, accounting for only 1.5% of cases.
Implications for Clinical Practice
"By understanding the factors contributing to SPM development and implementing effective monitoring strategies, health care providers can optimize patient outcomes and ensure the long-term safety of CAR T-cell therapies," the authors wrote. The findings underscore the importance of long-term monitoring and vigilance for SPMs in patients who have received CAR T-cell therapy, particularly those with a history of extensive prior treatments.
