Risk of Secondary Malignancies After Multiple Myeloma: A Nationwide Case-Control Cohort Study

Introduction: In light of improved survival rates among multiple myeloma (MM) survivors, we sought to assess their risk of secondary malignancies compared to the general population. Materials and Methods: This nationwide population-based case-control cohort study utilized the Korea National Health Insurance Service (KNHIS) database incorporating data from 2009 to 2020. We analyzed a total of 7348 patients diagnosed with MM in the case cohort. We selected a control group of 29,351 individuals from the general population without MM, employing a 1:4 propensity score matching approach. Matching criteria included age, sex, and comorbidities to ensure a balanced and reliable comparison. Results: The cumulative incidence of any secondary malignancy was significantly higher in the case cohort than the control cohort (Hazard ratio [HR] 1.576, 95% confidence interval [CI], [1.381-1.798]). Hematologic malignancy risk was notably higher in the case cohort (HR 8.026, 95% CI, [5.402-11.924]), especially therapy-related myeloid neoplasms (t-MN) (HR 12.063, 95% CI, [6.839-21.278]). No significant difference was shown in nonhematologic malignancy incidence. In subgroup analysis, transplant-eligible MM patients had a significantly higher incidence of any secondary malignancy (HR 1.104, 95% CI, [1.003-1.214]) than transplant-ineligible patients. The incidence of secondary malignancy in MM patients in the lenalidomide-available era was not significantly increased compared to the prelenalidomide era. Conclusion: While hematologic malignancies, particularly t-MN, are significantly elevated in MM patients compared to general population, nonhematologic malignancies do not appear to be significantly elevated.