NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Featured Updates to the NCCN Guidelines

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  • 1 Mayo Clinic Cancer Center;
  • 2 University of Wisconsin Carbone Cancer Center;
  • 3 Roswell Park Comprehensive Cancer Center;
  • 4 Stanford Cancer Institute;
  • 5 Fred & Pamela Buffett Cancer Center;
  • 6 University of Michigan Rogel Cancer Center;
  • 7 Dana-Farber/Brigham and Women’s Cancer Center;
  • 8 St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center;
  • 9 Vanderbilt-Ingram Cancer Center;
  • 10 UC San Diego Moores Cancer Center;
  • 11 The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute;
  • 12 Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute;
  • 13 Abramson Cancer Center at the University of Pennsylvania;
  • 14 O'Neal Comprehensive Cancer Center at UAB;
  • 15 Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance;
  • 16 City of Hope National Medical Center;
  • 17 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;
  • 18 Duke Cancer Institute;
  • 19 Memorial Sloan Kettering Cancer Center;
  • 20 UCSF Helen Diller Family Comprehensive Cancer Center;
  • 21 Patient Advocate;
  • 22 Massachusetts General Hospital Cancer Center;
  • 23 Huntsman Cancer Institute at the University of Utah;
  • 24 Robert H. Lurie Comprehensive Cancer Center of Northwestern University;
  • 25 Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine;
  • 26 Fox Chase Cancer Center;
  • 27 The University of Texas MD Anderson Cancer Center; and
  • 28 National Comprehensive Cancer Network.
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The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1.2020 version of the NCCN Guidelines for Multiple Myeloma.

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    International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749757.

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    Hillengass J, Moulopoulos LA, Delorme S, . Findings of whole body computed tomography compared with conventional skeletal survey in patients with monoclonal plasma cell disorders—a study of the International Myeloma Working Group. Blood 2016;128:44684468.

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    Hinge M, Andersen KT, Lund T, . Baseline bone involvement in multiple myeloma—a prospective comparison of conventional x-ray, low-dose computed tomography, and 18flourodeoxyglucose positron emission tomography in previously untreated patients. Haematologica 2016;101:e415418.

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    Kröpil P, Fenk R, Fritz LB, . Comparison of whole-body 64-slice multidetector computed tomography and conventional radiography in staging of multiple myeloma. Eur Radiol 2008;18:5158.

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    Princewill K, Kyere S, Awan O, . Multiple myeloma lesion detection with whole body CT versus radiographic skeletal survey. Cancer Invest 2013;31:206211.

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    Nanni C, Zamagni E, Farsad M, . Role of 18F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results. Eur J Nucl Med Mol Imaging 2006;33:525531.

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    Siontis G, Kumar S, Dispenzieri A, . Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J 2015;5:e364.

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    Zamagni E, Nanni C, Gay F, . 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease. Leukemia 2016;30:417422.

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    Hillengass J, Fechtner K, Weber MA, . Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol 2010;28:16061610.

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    Merz M, Hielscher T, Wagner B, . Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma. Leukemia 2014;28:19021908.

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    Bartel TB, Haessler J, Brown TL, . F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood 2009;114:20682076.

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    Moreau P, Attal M, Caillot D, . Prospective evaluation of magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography-computed tomography at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI 2009 trial: results of the IMAJEM study. J Clin Oncol 2017;35:29112918.

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    Walker R, Barlogie B, Haessler J, . Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol 2007;25:11211128.

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    Zamagni E, Nanni C, Mancuso K, . PET/CT improves the definition of complete response and allows to detect otherwise unidentifiable skeletal progression in multiple myeloma. Clin Cancer Res 2015;21:43844390.

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  • 18.

    Pawlyn C, Fowkes L, Otero S, . Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma? Leukemia 2016;30:14461448.

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  • 19.

    Rasche L, Alapat D, Kumar M, . Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma. Leukemia 2019;33:17131722.

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  • 20.

    Rasche L, Angtuaco E, McDonald JE, . Low expression of hexokinase-2 is associated with false-negative FDG-positron emission tomography in multiple myeloma. Blood 2017;130:3034.

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  • 21.

    Facon T, Kumar S, Plesner T, . Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 2019;380:21042115.

  • 22.

    Bringhen S, Petrucci MT, Larocca A, . Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood 2014;124:6369.

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  • 23.

    Bringhen S, D’Agostino M, De Paoli L, . Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. Leukemia 2018;32:979985.

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  • 24.

    Bringhen S, Mina R, Petrucci MT, . Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies. Haematologica 2019;104:16401647.

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  • 25.

    Boccia RV, Bessudo A, Agajanian R, . A multicenter, open-label, phase 1b study of carfilzomib, cyclophosphamide, and dexamethasone in newly diagnosed multiple myeloma patients (CHAMPION-2). Clin Lymphoma Myeloma Leuk 2017;17:433437.

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  • 26.

    Kumar SK, Buadi FK, LaPlant B, . Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma. Blood Cancer J 2018;8:70.

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  • 27.

    Dimopoulos MA, Grosicki S, Jędrzejczak WW, . All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Eur J Cancer 2019;106:8998.

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  • 28.

    Attal M, Lauwers-Cances V, Marit G, . Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:17821791.

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    McCarthy PL, Owzar K, Hofmeister CC, . Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:17701781.

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    Palumbo A, Hajek R, Delforge M, . Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012;366:17591769.

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    Hulin C, Belch A, Shustik C, . Updated outcomes and impact of age with lenalidomide and low-dose dexamethasone or melphalan, prednisone, and thalidomide in the randomized, phase III FIRST trial. J Clin Oncol 2016;34:36093617.

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  • 32.

    Holstein SA, Jung SH, Richardson PG, . Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial. Lancet Haematol 2017;4:e431442.

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  • 33.

    McCarthy PL, Holstein SA, Petrucci MT, . Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol 2017;35:32793289.

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  • 34.

    Goldschmidt H, Lokhorst HM, Mai EK, . Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia 2018;32:383390.

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  • 35.

    Sonneveld P, Schmidt-Wolf IG, van der Holt B, . Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol 2012;30:29462955.

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  • 36.

    Mellqvist UH, Gimsing P, Hjertner O, . Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood 2013;121:46474654.

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  • 37.

    Niesvizky R, Flinn IW, Rifkin RM, . Phase 3b UPFRONT study: safety and efficacy of weekly bortezomib maintenance therapy after bortezomib-based induction regimens in elderly, newly diagnosed multiple myeloma patients [abstract]. Blood 2010;116:Abstract 619.

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  • 38.

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

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  • 39.

    Dimopoulos MA, Gay F, Schjesvold F, . 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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  • 40.

    Chari A, Martinez-Lopez J, Mateos MV, . Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood 2019;134:421431.

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  • 41.

    Kumar SK, Grzasko N, Delimpasi S, . Phase 2 study of all-oral ixazomib, cyclophosphamide and low-dose dexamethasone for relapsed/refractory multiple myeloma. Br J Haematol 2019;184:536546.

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  • 42.

    Richardson PG, Oriol A, Beksac M, . Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol 2019;20:781794.

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    Mikhael JR, Reeder CB, Libby EN, . A phase I/II trial of cyclophosphamide, carfilzomib, thalidomide and dexamethasone (CYCLONE) in patients with newly diagnosed multiple myeloma: final results of MTD expansion cohort. Blood 2013;122:31793179.

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    Chari A, Vogl DT, Gavriatopoulou M, . Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med 2019;381:727738.

  • 45.

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    Knudsen LM, Hippe E, Hjorth M, . Renal function in newly diagnosed multiple myeloma—a demographic study of 1353 patients. Eur J Haematol 1994;53:207212.

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    Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Eur J Haematol 2000;65:175181.

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    Dimopoulos MA, Roussou M, Gavriatopoulou M, . Bortezomib-based triplets are associated with a high probability of dialysis independence and rapid renal recovery in newly diagnosed myeloma patients with severe renal failure or those requiring dialysis. Am J Hematol 2016;91:499502.

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    Dimopoulos MA, Sonneveld P, Leung N, . International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol 2016;34:15441557.

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    Dimopoulos MA, Christoulas D, Roussou M, . Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment. Eur J Haematol 2010;85:15.

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    Dimopoulos M, Weisel K, van de Donk NW, . Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and renal impairment: results from a phase II trial. J Clin Oncol 2018;36:20352043.

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  • 52.

    Ballester OF, Tummala R, Janssen WE, . High-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma and renal insufficiency. Bone Marrow Transplant 1997;20:653656.

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    Mahindra A, Hari P, Fraser R, . Autologous hematopoietic cell transplantation for multiple myeloma patients with renal insufficiency: a Center for International Blood and Marrow Transplant Research Analysis. Bone Marrow Transplant 2017;52:16161622.

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