The Changing Landscape of Second Primary Malignancies in Multiple Myeloma: A SEER Population-Based Study Between Two Therapeutic Eras.

Abstract

IntroductionThe introduction of proteasome inhibitors and immunomodulatory agents has significantly improved the prognosis of multiple myeloma (MM). However, the occurrence of second primary malignancies (SPMs) in MM survivors has raised widespread concern.MethodsThis population-based retrospective study using the SEER database analyzed data from 26,869 MM patients (1990-2021) to evaluate changes in SPMs across two therapeutic eras. Patients were stratified into two therapeutic eras based on the year of MM diagnosis: Era-1 (1990-2005; n=12,858) and Era-2 (2006-2021; n=14,011).ResultsAmong 1,346 MM patients who developed SPMs, 670 were in Era-1 and 676 in Era-2. The 15-year cumulative incidence of SPMs was significantly higher in Era-2 (7.7% vs. 4.8%, P < 0.001), an increase driven mainly by solid tumors (6.90% vs. 4.10%, P < 0.001) with no significant change in second hematological malignancies (0.84% vs. 0.67%, P = 0.13). Standardized incidence ratio (SIR) analysis revealed elevated hematological malignancy risk in Era-2 (SIR = 1.71, 95% CI: 1.49-1.96). Median time to SPM was shorter in Era-2 (43.5 vs. 59 months, P < 0.001). Notably, 80% of SPMs in Era-2 occurred within 90 months of MM diagnosis. Overall survival (OS) of SPM patients showed no significant improvement in Era-2 compared to Era-1. Within each diagnostic era, patients who developed SPMs exhibited longer overall survival than those with MM alone; however, this reflects survivor bias, as SPMs can only develop in patients who survive long enough after the initial MM diagnosis. No significant OS differences were observed among SPM patients by race or gender.ConclusionsThe risk of SPMs in MM survivors has significantly increased, and the latency between MM diagnosis and the onset of SPMs was shorter in the Era-2, highlighting the need for enhanced cancer surveillance in MM survivors.