Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies : an iSTOPMM study

Publisher Copyright: © 2023, The Author(s).Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG.Peer reviewe

Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.Black Swan Research Initiative by the International Myeloma Foundation Icelandic Centre for Research European Research Council (ERC) University of Iceland Landspitali University Hospita

Iceland screens, treats, or prevents multiple myeloma (iStopMM) : a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

Funding Information: P.K. is an employee of The Binding Site. BGMD has done consultancy for Amgen, Janssen, Celgene, Takeda. S.H. is the director of The Binding Site. O.L. has received research funding from: National Institutes of Health (NIH), National Cancer Institute (NCI), U.S. Food and Drug Administration (FDA), Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF), Leukemia and Lymphoma Society (LLS), Perelman Family Foundation, Rising Tide Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; Honoraria/ad boards: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data Monitoring Committees (IDMCs) for clinical trials lead by Takeda, Merck, Janssen, Theradex. S.Y.K. has received research funding from International Myeloma Foundation, European Research Council, Icelandic Center for Research (Rannís), Amgen, Celgene. The remaining authors declare no competing interests. Funding Information: The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation and the Icelandic Centre for Research (grant agreement No 173857). Furthermore, this project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 716677). Screening tests are performed by The Binding Site Ltd. Birmingham, UK. Additional funding is provided by the University of Iceland, Landspítali University Hospital, and the Icelandic Cancer Society. Crosslinking of study data to national registries is performed by the Icelandic Directorate of Health and the Icelandic Cancer Society. The study is made possible by the hundreds of nurses, laboratory technicians, and physicians around Iceland who collect blood samples from participants for screening or during follow-up and provide clinical care that is not part of the study. Icelandic and International myeloma patient organizations including Perluvinir, the Icelandic myeloma patient organization, and the International Myeloma Foundation have provided the project with important perspectives and networks. The information technology department and clinical laboratory staff at LUH made the complex sampling processes required for the study possible. The staff at Loftfar, Aton, Miðlun and Hvíta Húsið played an integral part in the development of recruiting strategies and media campaigns. Decode genetics have generously provided the study team with important insights and access to their state-of-the-art facilities. Presidents Vigdís Finnbogadóttir and Guðni Th Jóhannesson are thanked for their public support of the study. The iStopMM team including Sigurlína H Steinarsdóttir, Hera Hallbera Björnsdóttir, Tinna Hallsdóttir, Ingibjörg Björnsdóttir, and Eva Brynjarsdóttir are particularly acknowledged for their hard and dedicated work. Special thanks go to the residents of Akranes, Iceland who participated in the pilot and proof-of-concept of the study’s recruitment. Most importantly, acknowledgments go to the thousands of Icelanders who have generously provided their informed consent for the study, answered questionnaires, provided blood samples, and undergone diagnostic testing and follow-up. Publisher Copyright: © 2021, The Author(s).Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.Peer reviewe

Correction : Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies (Blood Cancer Journal, (2021), 11, 5, (94), 10.1038/s41408-021-00480-w)

Publisher Copyright: © The Author(s) 2023.In this article the author name Malin Hultcrantz was incorrectly written as Malin Hulcrantz. The original article has been corrected