Multiple myeloma diagnosis associated with markedly increased hematologic second primary malignancies in 279,894 patients.

BackgroundWith improving survival in multiple myeloma (MM), second primary malignancies (SPMs) remain an important issue in long-term care. This study assessed the risk of SPMs among individuals with MM.MethodsWe systematically searched EMBASE, PubMed, and the Cochrane Library for studies published up to August 15, 2025, and pooled standardized incidence ratios (SIRs) to compare SPM risks in MM patients with those in the general population.ResultsOf 1602 records screened, 15 studies comprising 279,894 MM patients met the inclusion criteria. The overall risks of SPMs and solid tumors were not significantly higher than those in the general population. In contrast, the risk of hematologic SPMs was markedly increased (SIR = 2.91; 95% CI: 1.57–5.41). Higher risks were identified for several malignancies, including non-Hodgkin lymphoma (NHL), myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), mesothelioma, skin cancer, melanoma, endocrine tumors, and thyroid cancer. Reduced risks were observed for chronic lymphocytic leukemia (CLL), head and neck cancer, tracheal/bronchial/lung cancer, bladder cancer, and breast cancer. Subgroup analyses showed no meaningful variation by diagnostic period, latency, age, or sex.ConclusionThese findings demonstrate that MM have a distinct SPM pattern, underscoring the need for tumor-specific surveillance with particular attention to hematologic SPMs and selected solid tumors. The lower incidence of breast cancer is an unexpected and potentially informative signal that could help guide future research. Overall, follow-up strategies should be shaped by site-specific risks rather than applied uniformly across all SPMs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251087056.