NCCN Guidelines® Insights: Multiple Myeloma, Version 3.2022

Featured Updates to the NCCN Guidelines

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  • 1 University of Wisconsin Carbone Cancer Center;
  • | 2 Fred & Pamela Buffett Cancer Center;
  • | 3 Robert H. Lurie Comprehensive Cancer Center of Northwestern University;
  • | 4 UT Southwestern Simmons Comprehensive Cancer Center;
  • | 5 University of Michigan Rogel Cancer Center;
  • | 6 Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center;
  • | 7 UC San Diego Moores Cancer Center;
  • | 8 The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute;
  • | 9 St. Jude Children's Research Hospital/The University of Tennessee Health Science Center;
  • | 10 Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute;
  • | 11 Abramson Cancer Center at the University of Pennsylvania;
  • | 12 O'Neal Comprehensive Cancer Center at UAB;
  • | 13 Roswell Park Comprehensive Cancer Center;
  • | 14 Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance;
  • | 15 City of Hope National Medical Center;
  • | 16 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;
  • | 17 Memorial Sloan Kettering Cancer Center;
  • | 18 Duke Cancer Institute;
  • | 19 UCLA Jonsson Comprehensive Cancer Center;
  • | 20 Stanford Cancer Institute;
  • | 21 UCSF Helen Diller Family Comprehensive Cancer Center;
  • | 22 Patient advocate;
  • | 23 Huntsman Cancer Institute at the University of Utah;
  • | 24 Moffitt Cancer Center;
  • | 25 Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine;
  • | 26 The University of Texas MD Anderson Cancer Center;
  • | 27 National Comprehensive Cancer Network; and
  • | 28 Mayo Clinic Cancer Center.

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.

  • 1.

    Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin 2021;71:733.

  • 2.

    National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Myeloma. Accessed November 24, 2021. Available at: https://seer.cancer.gov/statfacts/html/mulmy.html

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  • 3.

    Palumbo A, Bringhen S, Mateos MV, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 2015;125:20682074.

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  • 4.

    Landgren O, Hultcrantz M, Diamond B, et al. Safety and effectiveness of weekly carfilzomib, lenalidomide, dexamethasone, and daratumumab combination therapy for patients with newly diagnosed multiple myeloma: the MANHATTAN nonrandomized clinical trial. JAMA Oncol 2021;7:862868.

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  • 5.

    Costa LJ, Chhabra S, Godby KN, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) induction, autologous transplantation and post-transplant, response-adapted, measurable residual disease (MRD)-based Dara-Krd consolidation in patients with newly diagnosed multiple myeloma (NDMM) [abstract]. Blood 2019;134(Suppl 1):Abstract 860.

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  • 6.

    O’Donnell EK, Laubach JP, Yee AJ, et al. A phase 2 study of modified lenalidomide, bortezomib and dexamethasone in transplant-ineligible multiple myeloma. Br J Haematol 2018;182:222230.

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  • 7.

    O’Donnell EK, Laubach JP, Yee AJ, et al. Updated results of a phase 2 study of modified lenalidomide, bortezomib, and dexamethasone (RVd-lite) in transplant-ineligible multiple myeloma [abstract]. Blood 2019;134(Suppl 1):Abstract 3178.

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  • 8.

    Dimopoulos MA, Gay F, Schjesvold F, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2019;393:253264.

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  • 9.

    Dimopoulos MA, Špička I, Quach H, et al. Ixazomib as postinduction maintenance for patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplantation: the phase III TOURMALINE-MM4 trial. J Clin Oncol 2020;38:40304041.

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  • 10.

    Nooka AK, Kaufman JL, Muppidi S, et al. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia 2014;28:690693.

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  • 11.

    Joseph NS, Kaufman JL, Dhodapkar MV, et al. Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J Clin Oncol 2020;38:19281937.

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  • 12.

    Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet 2021;397:23612371.

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  • 13.

    Siegel DS, Schiller GJ, Samaras C, et al. Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment. Leukemia 2020;34:32863297.

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  • 14.

    Siegel DS, Schiller GJ, Samaras CJ, et al. Pomalidomide, dexamethasone, and daratumumab after lenalidomide treatment in relapsed refractory multiple myeloma: updated results from an open-label, multicenter, phase 2 trial [abstract]. Blood 2020;136(Suppl 1):1617.

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  • 15.

    Dimopoulos MA, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol 2021;22:801812.

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  • 16.

    Richardson PG, Oriol A, Larocca A, et al. Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma. J Clin Oncol 2021;39:757767.

  • 17.

    Schjesvold F, Robak P, Pour L, et al. OCEAN: a randomized phase III study of melflufen + dexamethasone to treat relapsed refractory multiple myeloma. Future Oncol 2020;16:631641.

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  • 18.

    Oncopeptides withdraws Pepaxto® in US, scale down organization and focus on R&D. Accessed November 24, 2021. Available at: https://www.oncopeptides.com/en/media/press-releases/oncopeptides-withdraws-pepaxto-in-us-scale-down-organization-and-focus-on-rd

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  • 19.

    Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021;384:705716.

  • 20.

    Kristinsson SY, Pfeiffer RM, Björkholm M, et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood 2010;115:49914998.

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  • 21.

    Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008;22:414423.

  • 22.

    Kristinsson SY. Thrombosis in multiple myeloma. Hematology (Am Soc Hematol Educ Program) 2010;2010:437444.

  • 23.

    Bradbury CA, Craig Z, Cook G, et al. Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials. Blood 2020;136:10911104.

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  • 24.

    Sanfilippo KM, Luo S, Wang TF, et al. Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score. Am J Hematol 2019;94:11761184.

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  • 25.

    Li A, Wu Q, Luo S, et al. Derivation and validation of a risk assessment model for immunomodulatory drug-associated thrombosis among patients with multiple myeloma. J Natl Compr Canc Netw 2019;17:840847.

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  • 26.

    Ikhlaque N, Seshadri V, Kathula S, et al. Efficacy of prophylactic warfarin for prevention of thalidomide-related deep venous thrombosis. Am J Hematol 2006;81:420422.

  • 27.

    Baz R, Li L, Kottke-Marchant K, et al. The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma. Mayo Clin Proc 2005;80:15681574.

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  • 28.

    Palumbo A, Cavo M, Bringhen S, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol 2011;29:986993.

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  • 29.

    Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019;380:711719.

  • 30.

    Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019;380:720728.

  • 31.

    Wang TF, Zwicker JI, Ay C, et al. The use of direct oral anticoagulants for primary thromboprophylaxis in ambulatory cancer patients: guidance from the SSC of the ISTH. J Thromb Haemost 2019;17:17721778.

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  • 32.

    Man L, Morris A, Brown J, et al. Use of direct oral anticoagulants in patients on immunomodulatory agents. J Thromb Thrombolysis 2017;44:298302.

  • 33.

    Storrar NPF, Mathur A, Johnson PRE, et al. Safety and efficacy of apixaban for routine thromboprophylaxis in myeloma patients treated with thalidomide- and lenalidomide-containing regimens. Br J Haematol 2019;185:142144.

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  • 34.

    Cornell RF, Goldhaber SZ, Engelhardt BG, et al. Apixaban for primary prevention of venous thromboembolism in patients with multiple myeloma receiving immunomodulatory therapy. Front Oncol 2019;9:45.

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  • 35.

    Pegourie B, Pernod G, Karlin L, et al. Evaluation of an oral direct anti-Xa anticoagulant, apixaban, for the prevention of venous thromboembolism in patients with myeloma treated with IMiD* compounds: a pilot study (MYELAXAT) [abstract]. J Clin Oncol 2017;35(Suppl):Abstract 8019.

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  • 36.

    van Doormaal FF, Raskob GE, Davidson BL, et al. Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. Thromb Haemost 2009;101:762769.

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  • 37.

    Piedra K, Peterson T, Tan C, et al. Comparison of venous thromboembolism incidence in newly diagnosed multiple myeloma patients receiving bortezomib, lenalidomide, dexamethasone (RVD) or carfilzomib, lenalidomide, dexamethasone (KRD) with aspirin or rivaroxaban thromboprophylaxis [published online August 15, 2021]. Br J Haematol, doi: 10.1111/bjh.17772

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