Second primary malignancies after CAR-T versus SCT in multiple myeloma.

e19556 Background: Multiple myeloma (MM) survival has improved with autologous stem cell transplantation (SCT) and immunotherapy, including chimeric antigen receptor T-cell (CAR-T) therapies, shifting attention towards late complications. As patients live longer, the incidence of second primary malignancies (SPMs) is an increasingly important survivorship issue. While SPMs have been documented in patients with MM, comparative data evaluating SPM risk among patients treated with CAR-T versus SCT alone remain limited. We compared the incidence of SPMs in MM patients treated with SCT and/or CAR-T using a large real-world database. Methods: We performed a retrospective cohort study using the TriNetX network. Two cohorts were constructed: Cohort (1) MM patients with SCT, without CAR-T therapy (MM-SCT-No CAR-T); and Cohort (2) MM patients with CAR-T with/without SCT (MM-CAR T+/- SCT ). Patients with non-MM malignancies prior to the index were excluded. The index date was the date of SCT or CAR-T administration. Propensity score matching was performed to balance baseline characteristics. Results: Mean follow-up was 949 and 314.5 days for cohorts 1 and 2 respectively. 263 patients in cohort 2 had received both SCT and CAR T. After propensity score matching, the analysis included 406 patients in each cohort, with balanced baseline characteristics. Secondary neoplasms occurred in 17 patients (4.25%) in cohort 1 and 83 patients (20.5%) in cohort 2 (risk difference -16.44% (-20.644,-11.843%); OR 0.172, 95% CI 0.1-0.296; HR 0.183 95% CI 0.109-0.309). Of these, 12 (2.97%) and 59 (14.568%) in cohorts 1 and 2 had hematologic malignancies (risk difference -11.598% (-15.411%,-7.784), OR 0.18, 0.095-0.34, HR 0.189 (0.101,0.351. Conclusions: In this real-world matched analysis, MM patients treated with CAR-T experienced a higher incidence of SPMs than those treated with SCT alone, particularly hematologic malignancies. These findings underscore the importance of incorporating secondary malignancy risk into long-term survivorship planning for CAR-T- treated patients and support the need for structured post-CAR-T surveillance and guideline-directed screening and treatment. Further studies are warranted to define therapy-specific and patient-level risk modifiers to guide the intensity and duration of long-term monitoring. Baseline characteristics of the two cohorts after matching. Characteristic MM-SCT-No CAR-T (N=406) MM with CAR-T +/- SCT (N=406) Standard difference Age at Index 66.2 +/- 8.8 66.7 +/- 8.9 0.049 Female 185 (45.5%) 175 (43.1%) 0.049 Male 221 (54.4%) 231 (56.8%) 0.049 Black or African American 90 (22.1%) 74 (18.2%) 0.098 White 273 (67.2%) 268 (66.0%) 0.026 Hispanic or Latino 10 (2.4%) 19 (4.6%) 0.119 Asian 10 (2.4%) 10 (2.4%) <0.001