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      Multiple myeloma current treatment algorithms

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      Blood Cancer Journal
      Nature Publishing Group UK
      Myeloma, Targeted therapies

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          Abstract

          The treatment of multiple myeloma (MM) continues to evolve rapidly with arrival of multiple new drugs, and emerging data from randomized trials to guide therapy. Along the disease course, the choice of specific therapy is affected by many variables including age, performance status, comorbidities, and eligibility for stem cell transplantation. In addition, another key variable that affects treatment strategy is risk stratification of patients into standard and high-risk MM. High-risk MM is defined by the presence of t(4;14), t(14;16), t(14;20), gain 1q, del(17p), or p53 mutation. In this paper, we provide algorithms for the treatment of newly diagnosed and relapsed MM based on the best available evidence. We have relied on data from randomized controlled trials whenever possible, and when appropriate trials to guide therapy are not available, our recommendations reflect best practices based on non-randomized data, and expert opinion. Each algorithm has been designed to facilitate easy decision-making for practicing clinicians. In all patients, clinical trials should be considered first, prior to resorting to the standard of care algorithms we outline.

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          Most cited references93

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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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            Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma.

            Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.
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              Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

              Background Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. Methods In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. Results At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10(5) white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. Conclusions The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).
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                Author and article information

                Contributors
                rajkumar.vincent@mayo.edu
                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group UK (London )
                2044-5385
                28 September 2020
                28 September 2020
                September 2020
                : 10
                : 9
                : 94
                Affiliations
                GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Division of Hematology, , Mayo Clinic, ; Rochester, MN USA
                Author information
                http://orcid.org/0000-0002-5862-1833
                http://orcid.org/0000-0001-5392-9284
                Article
                359
                10.1038/s41408-020-00359-2
                7523011
                32989217
                9253c2fd-403d-4e08-8a45-c6fd6597c9e5
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 July 2020
                : 11 August 2020
                : 20 August 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: CA 107476
                Award ID: CA 168762
                Award ID: CA 186781
                Award Recipient :
                Funded by: U.S. Department of Health & Human Services | National Institutes of Health (NIH)
                Funded by: U.S. Department of Health & Human Services | National Institutes of Health (NIH)
                Categories
                Current Treatment Algorithm
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                myeloma,targeted therapies
                Oncology & Radiotherapy
                myeloma, targeted therapies

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