Second Primary Malignancy Risk in Patients with Multiple Myeloma Receiving CAR T-Cell Therapy or Other Systemic Anticancer Treatments: A Real-World Comparative Study

PURPOSE: This study aims to compare the risk of second primary malignancy (SPM) between patients with multiple myeloma (MM) who received CAR T therapy versus other systemic anticancer therapies (SACTs). PATIENTS AND METHODS: Adult patients with MM who initiated CAR T therapy or other SACTs were identified from Komodo Health claims data and weighted to balance baseline characteristics. Cumulative incidence of SPM was estimated over 24 months, and P values calculated for difference between 0 and 24 months. RESULTS: The study included 435 patients who received CAR T therapy and 12,268 patients who received other SACTs (median follow-up: 11.8 months). Compared with other SACTs, CAR T therapy was associated with similar risks of any SPM (at 24 months: 24.1% vs. 22.3%,P0-24 mo's = 0.31) and solid SPM (9.1% vs. 11.5%, P0-24 mo's = 0.32), but significantly higher risk of hematologic SPM (17.9% vs. 13.1%, P0-24 mo's = 0.04). In a sensitivity analysis requiring ≥2 claims to identify an SPM, difference in hematologic SPM risk was attenuated (5.5% vs. 4.9%, P0-24 mo's = 0.08). Notably, bone marrow examinations were more common following CAR T therapy (e.g., 47% vs. 13% at 0-3 months). CONCLUSIONS: In this real-world dataset with relatively short follow-up, patients with MM appeared to have a higher risk of hematologic SPM following CAR T therapy compared with other SACTs. However, misclassification and detection bias cannot be ruled out. The association warrants further evaluation. Physicians should be vigilant for myeloid malignancies after CAR T therapy.