Tom 5, Nr 5 (2020)
Artykuły przeglądowe / Review articles
Opublikowany online: 2020-08-18

dostęp otwarty

Wyświetlenia strony 604
Wyświetlenia/pobrania artykułu 205
Pobierz cytowanie

Eksport do Mediów Społecznościowych

Eksport do Mediów Społecznościowych

Multiple myeloma – 2020 update on diagnosis and management

Grzegorz Charliński1, Artur Jurczyszyn2
Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory 2020;5(5):241-251.

Streszczenie

There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advances have necessitated a revision of the disease definition and staging of MM. Until recently, MM was defined by the presence of end-organ damage, specifically hypercalcemia, renal failure, anaemia, and bone lesions (CRAB features) that can be attributed to the clonal process. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria for MM to add three specific biomarkers that can be used to diagnose the disease in patients who did not have CRAB features: clonal bone marrow plasma cells greater than or equal to 60%, serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/l or higher, or more than one focal lesion on MRI. In addition, the definition was revised to allow CT and PET-CT to diagnose MM bone disease.

With the introduction of immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), major improvements have been achieved in the treatment and outcome of MM. Different treatment combinations are now in use and newer therapies are being developed. However, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of the relapsed disease remains a critical aspect of MM care and an important area of ongoing research. The aim of this review is to summarise the current methods of diagnosis and treatment of MM.

Artykuł dostępny w formacie PDF

Pokaż PDF Pobierz plik PDF

Referencje

  1. Palumbo A, Bringhen S, Ludwig H, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood. 2011; 118(17): 4519–4529.
  2. Jurczyszyn A, Nahi H, Avivi I, et al. Characteristics and outcomes of patients with multiple myeloma aged 21-40 years versus 41-60 years: a multi-institutional case-control study. Br J Haematol. 2016; 175(5): 884–891.
  3. Waszczuk-Gajda A, Szafraniec-Buryło S, Kraj L, et al. Epidemiology of multiple myeloma in Poland in the years 2008–2017. Arch Med Sci. 2020.
  4. Durie B, Hoering A, Abidi M, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017; 389(10068): 519–527.
  5. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017; 376(14): 1311–1320.
  6. Jurczyszyn A, Grzasko N, Gozzetti A, et al. Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice. Am J Hematol. 2016; 91(6): 575–580.
  7. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009; 113(22): 5412–5417.
  8. Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007; 356(25): 2582–2590.
  9. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23(12): 2210–2221.
  10. Rajkumar S, Dimopoulos M, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. The Lancet Oncology. 2014; 15(12): e538–e548.
  11. Rajkumar S. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2016(36): e418–e423.
  12. Terpos E, Kleber M, Engelhardt M, et al. European Myeloma Network. European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica. 2015; 100(10): 1254–1266.
  13. Russell SJ, Rajkumar SV. Multiple myeloma and the road to personalised medicine. Lancet Oncol. 2011; 12(7): 617–619.
  14. Greipp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma. J Clin Oncol. 2005; 23(15): 3412–3420.
  15. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015; 33(26): 2863–2869.
  16. Mikhael JR, Dingli D, Roy V, et al. Mayo Clinic. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013; 88(4): 360–376.
  17. Kumar S, Paiva B, Anderson K, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. The Lancet Oncology. 2016; 17(8): e328–e346.
  18. Moreau P, San Miguel J, Sonneveld P, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org, ESMO Guidelines Committee. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(suppl_4): iv52–iv61.
  19. Moreau P, Attal M, Facon T. Frontline therapy of multiple myeloma. Blood. 2015; 125(20): 3076–3084.
  20. Sonneveld P, Avet-Loiseau H, Lonial S, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016; 127(24): 2955–2962.
  21. Cavo M, Tacchetti P, Patriarca F, et al. GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010; 376(9758): 2075–2085.
  22. Reeder CB, Reece DE, Kukreti V, et al. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010; 115(16): 3416–3417.
  23. Sonneveld P, Schmidt-Wolf IGH, van der Holt B, et al. 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(24): 2946–2955.
  24. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017; 376(14): 1311–1320.
  25. Moreau P, Hulin C, Macro M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016; 127(21): 2569–2574.
  26. Moreau P, Avet-Loiseau H, Facon T, et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011; 118(22): 5752–8; quiz 5982.
  27. Mai EK, Bertsch U, Dürig J, et al. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015; 29(8): 1721–1729.
  28. Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment. J Clin Oncol. 2016; 34(13): 1544–1557.
  29. Kumar A, Kharfan-Dabaja MA, Glasmacher A, et al. Tandem versus single autologous hematopoietic cell transplantation for the treatment of multiple myeloma: a systematic review and meta-analysis. J Natl Cancer Inst. 2009; 101(2): 100–106.
  30. Attal M, Harousseau JL, Facon T, et al. InterGroupe Francophone du Myélome. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003; 349(26): 2495–2502.
  31. Mateos MV, Ocio EM, Paiva B, et al. Treatment for patients with newly diagnosed multiple myeloma in 2015. Blood Rev. 2015; 29(6): 387–403.
  32. McCarthy P, Holstein S, Petrucci M, et al. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol. 2017; 35(29): 3279–3289.
  33. Morgan GJ, Davies FE, Gregory WM, et al. NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011; 118(5): 1231–1238.
  34. Palumbo A, Gay F, Cavallo F, et al. MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012; 366(19): 1759–1769.
  35. Palumbo A, Bringhen S, Larocca A, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014; 32(7): 634–640.
  36. Mateos MV, Oriol A, Martínez-López J, et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012; 120(13): 2581–2588.
  37. Vincent Rajkumar S. Multiple myeloma: 2014 Update on diagnosis, risk-stratification, and management. Am J Hematol. 2014; 89(10): 999–1009.
  38. Facon T, Dimopoulos M, Dispenzieri A, et al. Initial Phase 3 Results Of The First (Frontline Investigation Of Lenalidomide + Dexamethasone Versus Standard Thalidomide) Trial (MM-020/IFM 07 01) In Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible For Stem Cell Transplantation (SCT). Blood. 2013; 122(21): 2–2.
  39. San Miguel JF, Schlag R, Khuageva NK, et al. VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008; 359(9): 906–917.
  40. Benboubker L, Dimopoulos MA, Dispenzieri A, et al. FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014; 371(10): 906–917.
  41. Fayers PM, Palumbo A, Hulin C, et al. Nordic Myeloma Study Group, Italian Multiple Myeloma Network, Turkish Myeloma Study Group, Hemato-Oncologie voor Volwassenen Nederland, Intergroupe Francophone du Myélome, European Myeloma Network. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011; 118(5): 1239–1247.
  42. Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017; 389(10068): 519–527.
  43. Pönisch W, Mitrou PS, Merkle K, et al. East German Study Group of Hematology and Oncology (OSHO). Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006; 132(4): 205–212.
  44. Rajkumar SV, Harousseau JL, Durie B, et al. International Myeloma Workshop Consensus Panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011; 117(18): 4691–4695.
  45. Cook G, Liakopoulou E, Pearce R, et al. British Society of Blood & Marrow Transplantation Clinical Trials Committee. Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant. 2011; 17(11): 1638–1645.
  46. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010; 116(23): 4745–4753.
  47. Mateos MV, Spencer A, Nooka AK, et al. ENDEAVOR Investigators, ELOQUENT-2 Investigators, Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007; 357(21): 2123–2132.
  48. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015; 372(2): 142–152.
  49. Siegel D, Dimopoulos M, Ludwig H, et al. Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2018; 36(8): 728–734.
  50. Mateos MV, Masszi T, Grzasko N, et al. TOURMALINE-MM1 Study Group. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016; 374(17): 1621–1634.
  51. Dimopoulos MA, San-Miguel J, Belch A, et al. POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016; 375(14): 1319–1331.
  52. Dimopoulos MA, Lonial S, Betts KA, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018; 124(20): 4032–4043.
  53. Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. The Lancet Oncology. 2013; 14(11): 1055–1066.
  54. Richardson P, Oriol A, Beksac M, et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. The Lancet Oncology. 2019; 20(6): 781–794.
  55. Dimopoulos MA, Lonial S, Betts KA, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018; 124(20): 4032–4043.
  56. Richardson PG, Sonneveld P, Schuster MW, et al. Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005; 352(24): 2487–2498.
  57. Dimopoulos MA, Moreau P, Palumbo A, et al. ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016; 17(1): 27–38.
  58. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017; 18(10): 1327–1337.
  59. Spencer A, Lentzsch S, Weisel K, et al. Daratumumab plus bortezomib and dexamethasone bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica. 2018; 103(12): 2079–2087.
  60. San-Miguel J, Hungria V, Yoon SS, et al. Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial. The Lancet Haematology. 2016; 3(11): e506–e515.
  61. Charlinski G. Treatment options for relapsed/refractory multiple myeloma in Poland within the reach of the Ministry of Health drug program in relation to European Society for Medical Oncology recommendations. Hematologia. 2020: in print [in Polish].
  62. Sonneveld P, Broijl A. Treatment of relapsed and refractory multiple myeloma. Haematologica. 2016; 101(4): 396–406.
  63. Ludwig H, Miguel JS, Dimopoulos MA, et al. International Myeloma Working Group recommendations for global myeloma care. Leukemia. 2014; 28(5): 981–992.