Background
Systematic review and meta-analysis of 15 studies comprising 279,894 multiple myeloma (MM) patients, assessing second primary malignancy (SPM) risk versus the general population. SPMs are an important survivorship concern given prolonged MM survival and exposure to alkylators, immunomodulatory drugs, and autologous transplant.
Interventions and follow up
Exposure group: MM patients from population-based and institutional cohorts
Comparator: age/sex-matched general population
Primary endpoint: Standardized incidence ratio (SIR) for SPMs and solid tumors
Median follow up: variable by study; pooled analysis across latency and age strata
Comparator: age/sex-matched general population
Primary endpoint: Standardized incidence ratio (SIR) for SPMs and solid tumors
Median follow up: variable by study; pooled analysis across latency and age strata
Results
Solid tumors overall: SIR not significantly elevated vs general population
Hematologic SPMs: SIR 2.91 (95% CI 1.57–5.41) — markedly increased risk
Elevated-risk malignancies: non-Hodgkin lymphoma, MDS, AML, mesothelioma, melanoma, thyroid cancer
Reduced-risk: breast cancer incidence lower than expected
Hematologic SPMs: SIR 2.91 (95% CI 1.57–5.41) — markedly increased risk
Elevated-risk malignancies: non-Hodgkin lymphoma, MDS, AML, mesothelioma, melanoma, thyroid cancer
Reduced-risk: breast cancer incidence lower than expected
Adverse events
Applicability: not applicable — observational meta-analysis with no study intervention
Clinical signal: the principal harm signal is the elevated SPM risk itself; surveillance is emphasized for high-risk malignancy subtypes
Clinical signal: the principal harm signal is the elevated SPM risk itself; surveillance is emphasized for high-risk malignancy subtypes
Conclusions
MM patients have a distinct second primary malignancy pattern, with hematologic SPMs carrying an approximately 3-fold increased risk. Selected solid tumors (melanoma, thyroid, mesothelioma) are elevated while breast cancer is reduced.
Key Limitations
Heterogeneity: variable study designs and follow-up periods limit pooling precision
Bias: publication bias possible; some malignancies may reflect surveillance bias
Causality: unclear whether SPMs reflect treatment exposure versus underlying disease biology
Bias: publication bias possible; some malignancies may reflect surveillance bias
Causality: unclear whether SPMs reflect treatment exposure versus underlying disease biology
Clinical Context
Informs long-term MM survivor care and supports risk-stratified surveillance by malignancy type rather than uniform screening, and guides counseling on treatment-related versus disease-related SPM risk. ASCO and ESMO survivorship frameworks endorse individualized secondary-cancer surveillance for MM survivors.