Risk for second primary malignancies in patients with multiple myeloma: a systematic review and meta-analysis

Our plain-English summary of Risk for second primary malignancies in patients with multiple myeloma: a systematic review and meta-analysis, by Y. Tian, L. Su, Y. Li, et al (Frontiers in Oncology, 2026).

The study

• Authors: Y. Tian, L. Su, Y. Li, M. Ye, Y. Zhang, Q. Li, Y. Jiao, J. Wu
• Journal: Frontiers in Oncology
• Published: 2026;16:1770120
• Type of article: Systematic review
• Read it: PubMed · Publisher · Free full text

Abstract

Background: With 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.

Methods: We 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.

Results: Of 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.

Conclusion: These 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 Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251087056.

Copyright © 2026 Tian, Su, Li, Ye, Zhang, Li, Jiao and Wu.

In plain English

This systematic review and meta-analysis compared how often second primary malignancies (new, separate cancers) occurred in people with multiple myeloma, a blood cancer, with the rate in the general population. It included 15 studies of 279,894 myeloma patients from America, Sweden, Finland, Korea, Spain and Germany. Pooled risks of any second cancer (standardized incidence ratio 1.07, 95% CI 0.97-1.18) and of solid tumors (0.97, 95% CI 0.75-1.26) were not significantly raised. The risk of second blood cancers was raised (2.91, 95% CI 1.57-5.41). Mesothelioma occurred more often (1.68, 95% CI 1.16-2.42), as did skin cancer, melanoma, endocrine and thyroid cancers, non-Hodgkin lymphoma, myelodysplastic syndromes and acute myeloid leukemia. Breast cancer (0.69, 95% CI 0.48-0.98) and chronic lymphocytic leukemia occurred less often. The authors cautioned that the leukemia result rested on two studies and the breast cancer result might reflect competing risk and screening effects. Results varied widely between studies. The article did not say whether the mesothelioma was pleural or peritoneal, or mention asbestos. The authors concluded that myeloma patients have a distinct pattern of second cancers needing site-specific monitoring, including for mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review and meta-analysis of published studies. Standardized incidence ratios were pooled with a random-effects model (PROSPERO CRD420251087056).
• Who was studied: 15 studies with a total of 279,894 multiple myeloma patients. Seven studies were from America, four from Sweden, two from Finland, and one each from Korea, Spain and Germany. Databases were searched from inception to August 15, 2025. The study periods ranged from 1935 to 2020.
• Exposure: Having multiple myeloma, compared with the expected cancer incidence in the general population. No asbestos or fiber exposure was studied.
• Main results:
  • Overall second primary malignancies in MM patients (10 studies): pooled SIR 1.07 (95% CI 0.97-1.18, P = 0.187), not significantly increased. Heterogeneity was substantial (I2 = 90.7%).
  • Hematologic second malignancies in MM patients (4 studies): pooled SIR 2.91 (95% CI 1.57-5.41, P = 0.001).
  • Solid tumor second malignancies in MM patients (6 studies): pooled SIR 0.97 (95% CI 0.75-1.26, P = 0.832), no significant difference from the general population.
  • Mesothelioma in MM patients: SIR 1.68 (95% CI 1.16-2.42; P = 0.006), significantly increased. The site of the mesothelioma and the number of contributing studies are not given in the main text.
  • Other increased solid tumor risks in MM patients: skin cancer SIR 2.64 (95% CI 1.80-3.85) and melanoma SIR 1.57 (95% CI 1.13-2.18).
  • Endocrine cancers in MM patients: SIR 1.73 (95% CI 1.08-2.79). Thyroid cancer: SIR 1.40 (95% CI 1.01-1.95).
  • Increased hematologic site risks in MM patients: non-Hodgkin lymphoma SIR 1.56 (95% CI 1.12-2.19), myelodysplastic syndromes SIR 57.9 (95% CI 25.08-133.67), and acute myeloid leukemia SIR 3.33 (95% CI 2.14-5.20).
  • Breast cancer in MM patients: SIR 0.69 (95% CI 0.48-0.98; P = 0.04), significantly reduced, based on 9 studies.
  • Chronic lymphocytic leukemia in MM patients: SIR 0.18 (95% CI 0.05-0.73), lower risk, based on only two studies.
  • Tracheal/bronchial/lung cancer: SIR 0.32, based on only two studies. When lung cancer was analyzed alone, incidence did not differ significantly.
  • Subgroup analyses by diagnosis year (before vs. after 2000), latency period, age at MM diagnosis and sex found no significant differences in overall SPM risk.
• The authors' conclusion: The authors concluded that patients with MM have a higher risk of hematologic second primary malignancies than the general population. They said monitoring should emphasize hematologic SPMs and key solid tumors, including mesothelioma.
• Limitations the authors state:
  • Substantial heterogeneity across pooled analyses, so the summary estimates should be interpreted with caution.
  • The included studies spanned the 1970s to the 2020s, a period in which MM treatment changed markedly.
  • The studies came from different regions and cancer registries, which may have affected case ascertainment and background incidence.
  • The original reports often lacked standardized information on treatment, MM subtype and disease stage.
  • Several reduced-risk estimates came from a small number of studies and may reflect heterogeneity, surveillance differences or incomplete ascertainment.
  • The lower breast cancer incidence may reflect competing risk and screening effects and needs further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Myeloma, Systematic Review, Meta-Analysis, Standardized Incidence Ratio (SIR), Mesothelioma, Lung Cancer, Latency.

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