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      Perspectives on the Risk-Stratified Treatment of Multiple Myeloma

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          Summary:

          The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.

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          Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma

          Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma.
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            Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group.

            The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM).
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              International staging system for multiple myeloma.

              There is a need for a simple, reliable staging system for multiple myeloma that can be applied internationally for patient classification and stratification. Clinical and laboratory data were gathered on 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe, and Asia. Potential prognostic factors were evaluated by univariate and multivariate techniques. Three modeling approaches were then explored to develop a staging system including two nontree and one tree survival assessment methodologies. Serum beta2-microglobulin (Sbeta2M), serum albumin, platelet count, serum creatinine, and age emerged as powerful predictors of survival and were then used in the tree analysis approach. A combination of Sbeta2M and serum albumin provided the simplest, most powerful and reproducible three-stage classification. This new International Staging System (ISS) was validated in the remaining patients and consists of the following stages: stage I, Sbeta2M less than 3.5 mg/L plus serum albumin > or = 3.5 g/dL (median survival, 62 months); stage II, neither stage I nor III (median survival, 44 months); and stage III, Sbeta2M > or = 5.5 mg/L (median survival, 29 months). The ISS system was further validated by demonstrating effectiveness in patients in North America, Europe, and Asia; in patients less than and > or = 65 years of age; in patients with standard therapy or autotransplantation; and in comparison with the Durie/Salmon staging system. CONCLUSION) The new ISS is simple, based on easy to use variables (Sbeta2M and serum albumin), and recommended for early adoption and widespread use.
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                Author and article information

                Journal
                Blood Cancer Discov
                Blood Cancer Discov
                Blood Cancer Discovery
                American Association for Cancer Research
                2643-3230
                2643-3249
                06 July 2022
                02 June 2022
                02 June 2022
                : 3
                : 4
                : 273-284
                Affiliations
                [1 ]Perlmutter Cancer Center, NYU Langone, New York, New York.
                [2 ]Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
                [3 ]The Royal Marsden Hospital, Department of Haematology, London, United Kingdom.
                [4 ]Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
                [5 ]Clinica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spain.
                [6 ]Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
                [7 ]Unité de Génomique du Myélome, Institut Universitaire du Cancer, Toulouse France. [8 ]Institut National de la Santé et de la Recherche Médicale, Paris, France.
                [9 ]The Multiple Myeloma Research Foundation, Norwalk, Connecticut.
                [10 ]Multiple Myeloma Center of Excellence, Icahn School of Medicine at Mt. Sinai, New York, New York.
                [11 ]Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
                [12 ]Erasmus MC Cancer Institute, Department of Hematology, Rotterdam, the Netherlands.
                [13 ]University Health Network and the Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
                [14 ]Department of Medicine, Mayo Clinic, Arizona.
                [15 ]Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
                [16 ]Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
                [17 ]Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, Arizona.
                [18 ]Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.
                [19 ]Myeloma Patients Europe, Brussels, Belgium.
                [20 ]Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
                [21 ]Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
                [22 ]Myeloma Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida.
                [23 ]Division of Hematology, University of Torino, Torino, Italy.
                [24 ]Department of Hematology, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium.
                [25 ]National University Cancer Institute, Singapore, Singapore. [26 ]Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. [27 ]NUS Centre for Cancer Research and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
                [28 ]Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology Oncology, Indiana University, Indianapolis, Indiana.
                [29 ]Department of Hematology, Mayo Clinic, Rochester, Minnesota.
                [30 ]Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
                Author notes
                [* ] Corresponding Author: Faith E. Davies, Clinical Myeloma Program, NYU Langone Perlmutter Cancer Center, New York, NY 10016. Phone: 212-263-4753; E-mail: Faith.davies@ 123456nyulangone.org

                Blood Cancer Discov 2022;3:273–84

                Author information
                https://orcid.org/0000-0002-3971-2393
                https://orcid.org/0000-0002-7190-0028
                https://orcid.org/0000-0002-9183-4857
                https://orcid.org/0000-0001-8791-1744
                https://orcid.org/0000-0003-1580-6106
                https://orcid.org/0000-0003-4481-5757
                https://orcid.org/0000-0003-1523-7388
                https://orcid.org/0000-0002-3677-4804
                https://orcid.org/0000-0003-4375-7399
                https://orcid.org/0000-0001-9670-2864
                https://orcid.org/0000-0002-5723-4129
                https://orcid.org/0000-0001-6485-4839
                https://orcid.org/0000-0002-8619-412X
                https://orcid.org/0000-0003-2578-8335
                https://orcid.org/0000-0002-0405-7480
                https://orcid.org/0000-0002-8615-6254
                https://orcid.org/0000-0001-5392-9284
                https://orcid.org/0000-0001-5362-2469
                https://orcid.org/0000-0002-6418-0886
                https://orcid.org/0000-0002-4271-6360
                Article
                BCD-21-0205
                10.1158/2643-3230.BCD-21-0205
                9894570
                35653112
                f3d3b515-8f7a-407e-b207-f3488910140f
                ©2022 The Authors; Published by the American Association for Cancer Research

                This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

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