Temporal trends in second primary malignancies among long-term survivors of multiple myeloma across treatment eras: a population-based analysis of the SEER database.

[OBJECTIVE] To evaluate temporal trends in second primary malignancy (SPM) risk among long-term multiple myeloma (MM) survivors across treatment eras.

[METHODS] This retrospective cohort study utilized the SEER 17 registries database (1975-2022). Patients with MM as first primary malignancy surviving ≥5 years were stratified into four treatment eras: Era 1 (≤2000, pre-novel agents), Era 2 (2001-2010, proteasome inhibitor/IMiD introduction), Era 3 (2011-2015, new-generation IMiDs), and Era 4 (2016+, daratumumab era). SPM was defined as any malignancy occurring ≥5 years post-diagnosis. Cumulative incidence was estimated using competing risk analysis.

[RESULTS] Among 52,497 MM patients, 15,402 (29.34%) achieved 5-year survival. Overall, 1,408 patients (9.14%) developed SPM over 72,951.70 person-years. SPM rates declined significantly across eras: 11.43% (Era 1), 10.45% (Era 2), 7.78% (Era 3), and 2.45% (Era 4) (P < 0.001). The most common SPMs were prostate (13.81%), lung (10.17%), and breast cancer (7.42%). Acute myeloid leukemia (6.78%) remained notable among hematologic malignancies. Sensitivity analysis among 10-year survivors confirmed the declining trend.

[CONCLUSIONS] SPM rates progressively declined from Era 1 through Era 3, with encouraging early signals in Era 4 requiring longer follow-up. The shift from alkylating agents to targeted therapies may contribute to reduced SPM occurrence, providing preliminary evidence for improved long-term safety of contemporary MM treatments.