Vol 52, No 2 (2021)
Review article
Published online: 2021-04-29
Role of transplantation in treatment of multiple myeloma in era of novel agents
Acta Haematol Pol 2021;52(2):77-84.
Abstract
Multiple myeloma (MM) is a B-cell malignancy characterized by clonal proliferation of plasma cells. Despite the introduction of novel agents such as immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies, high-dose chemotherapy with autologous transplantation remains the primary treatment for patients with newly diagnosed multiple myeloma. This review presents the results of clinical trials assessing the effectiveness and safety of various kinds of transplantation such as single, allogeneic, tandem and salvage. Nowadays, in the era of access to new therapies, the following questions should be asked: when is the best time to perform autologous transplantation? What is the significance of allogeneic or tandem transplantation? Is the use of a second or third salvage transplant justified? Will chimeric antigen receptor T-cell (CAR-T) therapy become a valuable therapeutic method in MM? In this article, we will try to answer these questions.
Keywords: multiple myelomanovel agentstransplantationautologousallogeneicCAR-T
References
- Röllig C, Knop S, Bornhäuser M. Multiple myeloma. Lancet. 2015; 385(9983): 2197–2208.
- Child JA, Morgan GJ, Davies FE, et al. Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003; 348(19): 1875–1883.
- Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996; 335(2): 91–97.
- Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014; 371(10): 895–905.
- Gay F, Oliva S, Petrucci MT, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015; 16(16): 1617–1629.
- Cavo M, Hájek R, Pantani L, et al. Autologous stem cell transplantation versus bortezomib-melphalan-prednisone for newly diagnosed multiple myeloma: second interim analysis of the phase 3 EMN02/HO95 Study. Blood. 2017; 130(Suppl 1): 397.
- Attal M, Lauwers-Cances V, Hulin C, et al. IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017; 376(14): 1311–1320.
- Jasielec JK, Kubicki T, Raje N, et al. Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma. Blood. 2020; 136(22): 2513–2523.
- Vij R, Wang M, Jagannath S, et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012; 119(24): 5661–5670.
- Moreau P, Attal M, Hulin C, et al. 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. Lancet. 2019; 394(10192): 29–38.
- Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136(8): 936–945.
- Ntanasis-Stathopoulos I, Gavriatopoulou M, Kastritis E, et al. Multiple myeloma: Role of autologous transplantation. Cancer Treat Rev. 2020; 82: 101929.
- 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.
- Martino M, Recchia AG, Fedele R, et al. The role of tandem stem cell transplantation for multiple myeloma patients. Expert Opin Biol Ther. 2016; 16(4): 515–534.
- Sonneveld P, van der Holt B, Segeren CM, et al. Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial. Haematologica. 2007; 92(7): 928–935.
- Mina R, Lonial S. Is there still a role for stem cell transplantation in multiple myeloma? Cancer. 2019; 125(15): 2534–2543.
- Hagen PA, Stiff P. The role of salvage second autologous hematopoietic cell transplantation in relapsed multiple myeloma. Biol Blood Marrow Transplant. 2019; 25(3): e98–e9e107.
- Cook G, Ashcroft AJ, Cairns DA, et al. National Cancer Research Institute Haemato-oncology Clinical Studies Group. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016; 3(7): e340–e351.
- Baertsch MA, Schlenzka J, Mai EK, et al. Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma. BMC Cancer. 2016; 16: 290.
- Garderet L, Iacobelli S, Koster L, et al. Outcome of a salvage third autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2018; 24(7): 1372–1378.
- Greil C, Engelhardt M, Ihorst G, et al. Allogeneic transplantation of multiple myeloma patients may allow long-term survival in carefully selected patients with acceptable toxicity and preserved quality of life. Haematologica. 2019; 104(2): 370–379.
- Garban F, Attal M, Michallet M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006; 107(9): 3474–3480.
- Rosiñol L, Pérez-Simón JA, Sureda A, et al. Programa para el Estudio y la Terapéutica de las Hemopatías Malignas y Grupo Español de Mieloma (PETHEMA/GEM). A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood. 2008; 112(9): 3591–3593.
- Giaccone L, Storer B, Patriarca F, et al. Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma. Blood. 2011; 117(24): 6721–6727.
- Gahrton G, Iacobelli S, Björkstrand Bo, et al. EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013; 121(25): 5055–5063.
- Bensinger W. Allogeneic stem cell transplantation for multiple myeloma. Hematol Oncol Clin North Am. 2014; 28(5): 891–902.
- Feinberg D, Paul B, Kang Y. The promise of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma. Cell Immunol. 2019; 345: 103964.
- Stirrups R. CAR T-cell therapy for relapsed or refractory multiple myeloma. Lancet Oncol. 2019; 20(6): e297.
- Lin Q, Zhao J, Song Y, et al. Recent updates on CAR T clinical trials for multiple myeloma. Mol Cancer. 2019; 18(1): 154.
- Dytfeld D. Chimeric antigen receptor T in the treatment of multiple myeloma – state of the art and future directions. Acta Haematol Pol. 2020; 51(3): 120–124.
