Second primary malignancy (SPM) in patients (pts) with multiple myeloma (MM) receiving chimeric antigen receptor T-cell (CAR T) therapy or other systemic anticancer therapy (SACT): A comparative study using a real-world database.
Authors: Attaya Suvannasankha, Mengying Li, Omonefe O. Omofuma, Christian Hampp, Matthew Phelan, Alexander Breskin, Ping Shao, Tito Roccia, Nandita Mukherjee, Anju Shrestha, Daniel Junseung Lee, Jacob Glass, Kate Knorr, Glenn Scott Kroog, Karen Rodriguez-Lorenc
Journal: Journal of Clinical Oncology (2025)

7519 Background: Cases of SPM have been reported following CAR T therapy, but comparative studies are scarce. We compared the risk of SPM following CAR T therapy vs other SACT in pts with MM. Methods: Pts aged ≥18 years with MM who initiated CAR T therapy or other SACT, except stem cell transplant, in second-line or beyond were identified from Komodo Health claims data (3/26/2021–1/31/2024). Incident SPM was identified by ≥1 diagnostic code through death, disenrollment, or data cutoff (4/30/2024), whichever was earliest. Cumulative incidence of SPM following CAR T therapy or other SACT was estimated through 24 months, weighted by baseline factors including prior MM treatments; p-values were calculated for differences in the area under the curves through 24 months. Results: Pts who received CAR T therapy (n=436) or other SACT (n=18,603) were followed for a median of 11.8 months (IQR 5.7–22.8). Compared to pts who received other SACT, pts who received CAR T therapy had nominally higher risk (cumulative incidence [95% CI]) of any SPM (p = 0.05; 24.1% [18.4%, 29.8%] vs. 18.1% [13.5%, 22.8%] at 24 months), driven by significantly higher heme SPM risk (p=0.01; 8.7% [6.1%, 11.4%] vs. 5.6% [3.0%, 8.8%] at 6 months, 12.1% [8.7%, 15.3%] vs. 7.2% [4.3%, 10.4%] at 12 months, and 17.9% [12.8%, 23.5%] vs. 8.7% [5.4%, 11.7%] at 24 months; respectively), including higher risks of myelodysplastic syndrome and leukemias. The risk of solid SPM was nominally lower following CAR T vs other SACT (p=0.28; 9.1% [6.2–12.3] vs 13.9% [9.6–18.4] at 24 months). In the sensitivity analysis requiring ≥2 diagnostic codes to identify an SPM, the absolute risk was reduced and the difference in heme SPM risk was attenuated (p=0.39; Table). Notably, pts were more likely to receive bone marrow examination following CAR T therapy vs other SACT (47% vs 10% at 0–3 months, respectively). Conclusions: Pts with MM appeared to have a higher risk of heme SPM through 24 months following CAR T therapy compared with other SACT. However, the difference was attenuated in a sensitivity analysis that required ≥2 diagnostic codes, assumed to represent a confirmed diagnosis. Potential detection bias may exist, suggested by a higher rate of bone marrow examination following CAR T therapy. Longer term studies are needed to further evaluate this association. Cumulative incidence (%) and 95% CI of SPM at 24 months. SPM Analysis CAR T therapy Other SACT p-value Any Main 24.1 (18.4–29.8) 18.1 (13.5–22.8) 0.05 Sensitivity 11.5 (8.1–15.1) 9.5 (6.3–13.2) 0.10 Heme Main 17.9 (12.8–23.5) 8.7 (5.4–11.7) 0.01 Sensitivity 5.5 (3.4–7.6) 4.7 (2.3–7.6) 0.39 Solid Main 9.1 (6.2–12.3) 13.9 (9.6–18.4) 0.28 Sensitivity 6.4 (3.8–9.7) 5.1 (3.0–8.4) 0.14 Sensitivity analysis requires 2+ diagnostic codes to identify an SPM.