Multiple myeloma (MM) is a debilitating malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Grignani G, Gobbi PG, Formisano R, et al. Kristinsson SY, Pfeiffer RM, Bjrkholm M, et al. Dimopoulos MA, Dytfeld D, Grosicki S, et al. In addition, other cytogenetic changes termed secondary cytogenetic abnormalities arise along the disease course of multiple myeloma, including gain(1q), del(1p), del(17p), del(13), and secondary translocations involving MYC. Save 2.20. government site. Use of the European Organisation for Research and Treatment of Cancer multiple myeloma module (EORTC QLQ-MY20): a review of the literature 25 years after development. The revised International Myeloma Working Group (IMWG) criteria for the diagnosis of multiple myeloma and related disorders are shown on Table 1.1 The diagnosis of multiple myeloma requires the presence of one or more myeloma defining events (MDE) in addition to evidence of either 10% or more clonal plasma cells on bone marrow examination or a biopsy-proven plasmacytoma. Moreau P, San Miguel J, Ludwig H, Schouten H, Mohty M, Dimopoulos M, Dreyling M; ESMO Guidelines Working Group. When multiple myeloma is suspected clinically, patients should be tested for the presence of M proteins using a combination of tests that should include a serum protein electrophoresis (SPEP), serum immunofixation (SIFE), and the serum FLC assay.24 Approximately 2% of patients with multiple myeloma have true non-secretory disease and have no evidence of an M protein on any of the above studies.6,25 Bone marrow studies at the time of initial diagnosis should include fluorescent in situ hybridization (FISH) probes designed to detect t(11;14), t(4;14), t(14;16), t(6;14), t(14;20), trisomies, and del(17p) (see Risk-Stratification below).26 Conventional karyotyping to detect hypodiploidy and deletion 13 has value, but if FISH studies are done, additional value in initial risk-stratification is limited. Management of Teclistamab associated cytokine release syndrome (CRS) and neurotoxicity. Patients with more aggressive relapse with plasma cell leukemia or extramedullary plasmacytomas often require therapy with a multi-drug anthracycline containing regimen such as VDT-PACE. Rajkumar SV, Richardson PG, Hideshima T, Anderson KC. Physician Assistants: NCCN has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. Khorana AA, Soff GA, Kakkar AK, et al. Both arms received lenalidomide maintenance for one year. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Attal M, Harousseau JL, Stoppa AM, et al. Careers. Siegel DS, Schiller GJ, Samaras C, et al. mSMART guidelines are ranked pretty high in Google. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Derivation and validation of a risk assessment model for immunomodulatory drug-associated thrombosis among patients with multiple myeloma. Mayo Clin Proc 2005;80:15681574. Expert medical clinical judgment is required when applying these guidelines in the context of individual clinical circumstances to provide optimal care. We also need additional data to determine if MRD negativity can be used as a surrogate endpoint for regulatory approval, and if sustained MRD negativity may be a marker of cure in at least a subset of patients.35, Typically, patients are treated with approximately 3-4 cycles of induction therapy prior to stem cell harvest. Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. J Clin Oncol;2015;33:2863-2869. Use of prophylactic anticoagulation agents may be considered if the risk of VTE is deemed high, particularly with IMiD-based induction therapy.21,26,27 One phase III trial has evaluated VTE prophylaxis specifically in patients with newly diagnosed MM undergoing treatment with thalidomide-based regimens. The panel received several requests to provide additional guidance in therapy selection for relapsed/refractory (R/R) MM. In the first nonrandomized clinical trial in patients with newly diagnosed multiple myeloma (n=41),4 daratumumab/carfilzomib/lenalidomide/dexamethasone therapy was associated with high rates of minimal residual disease (MRD) negativity (29 of 41 evaluable patients were MRD-negative after 8 cycles of therapy).4 At 11 months of the median follow-up, the trial reported 1-year progression-free survival (PFS) and overall survival (OS) rates of 98% (95% CI, 93%100%) and 100%, respectively.4. mSMART is constantly updated and evidence-based. Pharmacists: NCCN designates this knowledge-based continuing education activity for 1.0 contact hour (0.1 CEUs) of continuing education credit. Definitions and risk stratification models have become more sophisticated, with prognostication tailored to include high-risk cytogenetics as per the most recent International Myeloma Working Group 2020 risk model. This year, the panel has noted that for elderly patients with MM, an assessment of frailty or calculation of frailty score is recommended using the tool developed by the International Myeloma Working Group (http://www.myelomafrailtyscorecalculator.net/) to predict mortality and the risk of toxicity3 (see MYEL-F, page 10). The most common adverse reactions with isatuximab-irfc were infusion-related reactions, fatigue, hypertension, diarrhea, upper respiratory tract infection, pneumonia, dyspnea, and bronchitis. Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades, Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis, Review of 1,027 patients with newly diagnosed multiple myeloma. Mayo Clinic Proceedings. Would you like email updates of new search results? MM accounts for approximately 1.8% of all cancers and 18.7% of hematologic malignancies in the United States.1 MM is most frequently diagnosed among people aged 65 to 74 years, with the median age being 69 years.2 The American Cancer Society has estimated 34,920 new MM cases will be diagnosed in the United States in 2021, with an estimated 12,410 deaths.1. Palumbo A, Chanan-Khan A, Weisel K, et al. The updated criteria represent a paradigm shift since they allow early diagnosis and initiation of therapy before end-organ damage. J Clin Oncol 2017;35(Suppl):Abstract 8019. van Doormaal FF, Raskob GE, Davidson BL, et al. We believe by following our treatment recommendations we can narrow the outcomes gap between low- and high-risk patients. First described in 1848, MM is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein (M protein). Am J Hematol 2019;94:11761184. All of the relevant financial relationships listed have been mitigated. Landgren O, Hultcrantz M, Diamond B, et al. Based on these data, NCCN Guidelines included melphalan flufenamide/dexamethasone as a treatment option for patients with late relapses (4 prior therapies) and whose disease was refractory to at least one PI, one IMiD, and one CD38-directed monoclonal antibody. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Thrombosis in multiple myeloma. Dimopoulos MA, Gay F, Schjesvold F, et al. Single-agent daratumumab in heavily pre-treated patients with Multiple Myeloma: An Open-Label, International, Multicentre Phase 2 trial (Sirius), A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma, Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study, Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma, Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study, Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma, Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. 2023 Feb;12(1):1-6. doi: 10.14740/jh1085. Lonial S, Dimopoulos M, Palumbo A, et al. Alkharabsheh O, Bellman P, Mahmoudjafari Z, Cui W, Atrash S, Paul B, Hashmi H, Shune L, Ahmed N, Abdallah AO. This activity is designated for 1.0 AAPA Category 1 CME credit. Nevertheless, these estimates are valuable benchmarks, and appear generalizable to newly diagnosed myeloma patients in good performance status.47. This page contains general principles for consideration, screening and prophylaxis recommendations, important dosing and administration considerations, and a few noteworthy side effects and laboratory testing considerations. This activity is supported by a medical education grant from Karyopharm Therapeutics. Elotuzumab, a monoclonal antibody targeting the signaling lymphocytic activation molecule F7 (SLAMF7).82 Unlike daratumumab, elotuzumab does not have single-agent activity but shows synergistic activity when combined with Rd (Table 8).82 Elotuzumab is well tolerated, and was initially approved in 2015 by the FDA to be given in combination with Rd for the treatment of patients with multiple myeloma who have received one to three prior therapies. Scientific advisor for Karyopharm Therapeutics, Bristol-Myers Squibb/Celgene, Janssen Research & Development, LLC, Oncopeptides, and Sanofi-Genzyme; and honoraria from Karyopharm Therapeutics, Cardinal Health Specialty Solutions, and CurioScience. Based on the results of the IKEMA trial, the panel included isatuximab-irfc/carfilzomib/dexamethasone as a category 1, preferred regimen option for patients with R/R MM. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. We decided we should think in these terms: "If we personally or our loved one had multiple myeloma, what should we be doing for that patient, and what should our general recommendations be?". For patients with MM, risk scores may be obtained using 2 scoring systems. Siegel DS, Schiller GJ, Samaras CJ, et al. Cornell RF, Goldhaber SZ, Engelhardt BG, et al. In one randomized trial, daratumumab, bortezomib, thalidomide, dexamethasone (Dara-VTd) showed superior response rates, PFS, and a trend to better OS compared with VTd.88 A randomized phase II trial has found that daratumumab plus VRd (Dara-VRd) increases the rate and depth of response to therapy and prolongs PFS compared with VRd.107 In these trials, as expected, the benefit of daratumumab in terms of surrogate endpoints was more pronounced in the standard risk patients, a positive effect was nevertheless seen in both standard and high risk disease. Accessibility Non-IgM monoclonal gammopathy of undetermined significance (MGUS), IgM Monoclonal gammopathy of undetermined significance (IgM MGUS), Solitary Plasmacytoma with minimal marrow involvement, Recurrent trisomies involving odd-numbered chromosomes with the exception of chromosomes 1, 13, and 21, Intermediate-risk of progression, median TTP of 3 years, Good prognosis, standard-risk MM, median OS 7-10 years, Standard-risk of progression, median TTP of 5 years, High-risk of progression, median TTP of 2 years, Trisomies plus any one of the IgH translocations, May ameliorate adverse prognosis conferred by high risk IgH translocations, and del 17p, Isolated Monosomy 13, or Isolated Monosomy 14, Low-risk of progression, median TTP of 7-10 years, Good prognosis, probably reflecting low tumor burden, median OS >7-10 years, Bortezomib-Thalidomide-Dexamethasone (VTd), Bortezomib- Cyclophosphamide-Dexamethasone, Bortezomib-Lenalidomide-Dexamethasone (VRd), Carfilzomib- Cyclophosphamide-Dexamethasone (KCd), Carfilzomib-Lenalidomide-Dexamethasone (KRd), Carfilzomib-Pomalidomide-Dexamethasone (KPd), Daratumumab-Lenalidomide-Dexamethasone (DRd), Daratumumab 16 mg/ kg intravenously weekly x 8 weeks, and then every 2 weeks for 4 months, and then once monthly, Daratumumab-Bortezomib-Dexamethasone (DVd), Daratumumab-Pomalidomide-Dexamethasone (DPd), Daratumumab-Carfilzomib-Dexamethasone (DKd), Daratumumab 1800 mg subcutaneously (or 16 mg/ kg intravenously) weekly x 8 weeks, and then every 2 weeks for 4 months, and then once monthly, Ixazomib-Lenalidomide-Dexamethasone (IRd), Elotuzumab-Pomalidomide-Dexamethasone (EPd), 10 mg/ kg intravenously weekly x 8 weeks, and then 20 mg/kg every 4 weeks, Isatuximab-Pomalidomide-Dexamethasone (Isa-Pd), 10 mg/ kg intravenously weekly x 4 weeks, and then every 2 weeks, Isatuximab-carfilzomib-Dexamethasone (Isa-Kd), Serum free light chain ratio (involved/uninvolved) >20, Progressive increase in M protein level (Evolving type of SMM), MRI with diffuse abnormalities or with 1 focal lesion, PET-CT with focal lesion with increased uptake but without underlying osteolytic bone destruction. 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