Page 236 - Haematologica Vol. 109 - July 2024

ARTICLE - Plasma Cell Disorders
Prior cancer and risk of monoclonal gammopathy of undetermined significance: a population-based study in Iceland and Sweden
Sæmundur Rögnvaldsson,1,2 Sigrun Thorsteinsdóttir,1,3 Elisavet Syriopoulou,4,5 Ingigerdur Sverrisdottir,1,6 Ingemar Turesson,7 Elias Eythorsson,1,2 Jon Thorir Oskarsson,1 Thorir Einarsson Long,1,7 Brynjar Vidarsson,2 Pall Torfi Onundarson,1,2 Bjarni A. Agnarsson,1,2 Margret Sigurdardottir,2 Isleifur Olafsson,2 Ingunn Thorsteinsdottir,2 Thor Aspelund,1 Gauti Kjartan Gislason,1 Andri Olafsson,1 Jon Kristinn Sigurdsson,1 Malin Hultcrantz,8 Brian G. M. Durie,9 Stephen Harding,10 Magnus Bjorkholm,4,11 Ola Landgren,12 Thorvardur Jon Love1,2 and Sigurdur Yngvi Kristinsson1,2
1Faculty of Medicine, University of Iceland, Reykjavík, Iceland; 2Landspítali – The National University Hospital of Iceland, Reykjavík, Iceland; 3Rigshospitalet, Copenhagen, Denmark; 4Karolinska Institutet, Stockholm, Sweden; 5Red Door Analytics AB, Stockholm, Sweden; 6Sahlgrenska University Hospital, Gothenburg, Sweden; 7Skåne University Hospital, Lund, Sweden; 8Myeloma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 9Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA, USA; 10Binding Site Group Ltd., Birmingham, UK; 11Karolinska University Hospital, Stockholm, Sweden and 12Myeloma Program, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA
Abstract
There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with a higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might there- fore constitute a target population for MGUS screening. This two-part study is the first study to evaluate a relationship between MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio=1.10; 95% confidence interval: 1.00-1.20). This excess risk was lim- ited to prior cancers in the year preceding MGUS screening. A history of prior cancer was associated with progression of MGUS, except for myeloid malignancies which were associated with a lower risk of progression (hazard ratio=0.37; 95% confidence interval: 0.16-0.89; P=0.028). Our findings indicate that a prior cancer is not a significant etiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a pri- or cancer.
Introduction
Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM), Waldenström macroglobulinemia (WM), and other lymphoproliferative disorders (LPD).1,2 MGUS is common in the general population with a prevalence of 4.2% in subjects over the age of 50 years, but only in 0.5-1.5% per year does the MGUS progress to active malignancy.2-4 The
causes of MM, WM and other LPD are poorly understood but both genetic5 and environmental6,7 causes have been implicated. Importantly, because MGUS is the precursor of MM, WM, and related LPD, the etiology of these malig- nancies would be expected to involve the development or progression of MGUS.
Having cancer increases the risk of a second primary ma- lignancy8 but MM and WM are usually not considered as second primary malignancies. Theoretically, various factors
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Correspondence: S. Rögnvaldsson srognvald@hi.is
Received: Accepted: Early view:
September 25, 2023. January 4, 2024. January 11, 2024.
https://doi.org/10.3324/haematol.2023.284365
©2024 Ferrata Storti Foundation Published under a CC BY-NC license