P-468: Risk of Secondary Primary Malignancies after Multiple Myeloma in the Novel Therapy Era : A Nationwide Case-Control Cohort Study

Introduction: The introduction of novel agents for multiple myeloma (MM) has significantly improved survival rates. However, with improved overall survival, the development of subsequent second malignancies has become increasingly significant. Despite this, data describing the risk of secondary primary malignancies following MM diagnosis are scarce. This study aimed to compare the risk of secondary malignancy in MM patients to the general population at a nationwide population-based level.

Methods: We utilized the Korea National Health Insurance Service (KNHIS) database. 37,883 patients diagnosed with MM between January 2009 to December 2020, were selected. Landmark analyses at 1, 3, and 5-year were performed to minimize immortality bias and observe long-term trends. After refining the dataset by age (>19 years), diagnosis repetition, and excluding malignancies within the landmark period, 7,348 MM patients were included in the case cohort. Additionally, 29,351 individuals without MM were matched as controls using 1:4 propensity score matching based on age, sex, and comorbidities. Cumulative incidence of secondary malignancy was compared using the Gray test, treating death as a competing risk. Incidences of secondary malignancy and subtypes were compared, and hazard ratios (HR) were computed using the Fine-Gray subdistribution hazard model. Subgroup analysis based on transplant eligibility was conducted to explore the impact of high dose chemotherapy for autologous stem cell transplantation on the secondary malignancy occurrence.

Results: Median follow-up was 45.6 months for cases and 51.3 months for controls. The 10-year cumulative incidence rate of any secondary malignancy was significantly higher in cases than controls (10.52% vs. 8.68%, p< 0.001, HR 1.58, 95% confidence interval [CI] 1.38-1.80). The risk of hematologic malignancy was significantly higher in cases than controls (HR 8.03, 95% CI 5.40-11.92; 10-year incidence 2.34% vs. 0.36%, p< 0.001). Notably, the incidence of therapy-related myeloid neoplasms (t-MN) was significantly higher in cases (HR 12.06, 95% CI 6.84-21). There were no significant differences in the 10-year cumulative incidence of non-hematologic malignancy (6.17% vs. 8.29%, p=0.122, HR 0.9) or its subtypes. In the subgroup analysis, any secondary malignancy had significantly increased in the transplant-eligible MM patients compared to transplant-ineligible patients (p < 0.001).

Conclusions: The incidence of secondary solid malignancies did not differ markedly between MM cases and controls. However, the risk of hematologic malignancy and t-MN in MM patients was significantly higher compared to the general population. Transplant-eligible MM patients had a higher risk of developing any malignancies, suggesting that stem cell transplantation might be an important factor associated with the development of secondary malignancies in patients with MM.