Page 240 - Haematologica Vol. 109 - July 2024

ARTICLE - Prior cancers and risk of MGUS
S. Rögnvaldsson et al.
observed association is unclear. Secondly, although the total number of prior cancers was high, some cancer subtypes remained rare, precluding the detection of any rare cancer subtype-specific risks. However, due to the size of the study such associations are unlikely to hold much clinical significance. Thirdly, the study data did not include many prior cancers after the advent of immuno-oncology and targeted therapies23,24 which may affect the risk of MGUS or its progression in ways different from those of conventional therapies. Fourthly, the study populations are genetically and ethnically homogenous which may affect the nature of the prior cancers and may limit the generalizability of the results. Finally, all participants in the iStopMM study had to consent to MGUS screening and those with a prior cancer might be more or less likely to want to undergo screening; however, effect is non-differential between the groups in the analysis and should not have affected the overall result.
In conclusion, in this large study based on two comple- mentary population-based cohorts, we found that a recent history of cancer was associated with a modest increase in the prevalence of MGUS. However, prior cancer was not associated with the risk of MGUS progression. This associa- tion is unlikely to be causal or to be of clinical significance. Based on these findings we conclude that MM, WM, and other LPD preceded by MGUS are not significant second primary malignancies. The findings do not warrant surveil- lance of those with prior cancer for plasma cell disorders or differential management of MGUS in those with a prior cancer. The study provides robust evidence against the hy- pothesis that prior cancers and associated therapies cause plasma cell disorders and can help guide the attention of investigators towards other potential risk factors that could improve our understanding of the pathogenesis of plasma cell disorders and lead to potential avenues of prevention.
Disclosures
MB has been part of a grant committee for Incyte; sat on educational program committees for Roche, Pfizer, and Bristol-Myers Squibb; acted as a consultant or advisor for Janssen-Cilag and Schain Research; and received a research grant from Takeda. MH has received research grants from Amgen, GlaxoSmithKline and Daiichi Sankyo Company; and has acted as a consultant or advisor for Bristol-Meyers Squibb, Curio Science, GlaxoSmithKline, and Intellisphere. SH is currently employed at The Binding Site Ltd. OL has received research funding from the National Cancer Institute/ National Institutes of Health, Food and Drug Administra- tion, Leukemia & Lymphoma Society, Rising Tide Founda- tion, Multiple Myeloma Research Foundation, International Myeloma Foundation, Paula and Rodger Riney Foundation, Tow Foundation, Myeloma Solutions Fund, Perelman Family Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, and Karyopharm; has received honoraria for scientific talks or participated in advisory boards for Adap- tive, Amgen, Binding Site, Bristol-Meyers Squibb, Celgene, Cellectis, Glenmark, Janssen, Juno, and Pfizer; and has sat on independent Data Monitoring Committees for Takeda, Merck, and Janssen. SYK has received research funding from Amgen and Celgene; and has sat on an independent Data Monitoring Committee for Jansen.
Contributions
SR conceived the study and its design with further input from ST, IS, EE, JTO, TEL, and SYK. Data were analyzed by SR and ES. ITu, MB, and SYK collected data from Sweden. GKG, AO, and JKS curated data with supervision from TA. SYK supervised the project and the iStopMM study. SR, ST, IS, EE, JTO, TEL, BV, PTO, BAA, MS, IO, ITh, MH, BGMD, SH, OL, TJL, and SYK are part of the iStopMM team of investigators. All co-authors had access to and edited the manuscript.
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Figure 3. A forest plot of hazard ratios for risk of pro- gression of monoclonal gammopathy of undetermined significance for those with any type of prior cancer and by prior cancer subtype. HR: hazard ratio; CI: confidence interval.