American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma

Abstract

In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT" therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease. Regarding allogeneic HCT, the expert committee agreed on the following consensus statements: (1) Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be performed in the context of a clinical trial if possible; (3) The role of postallogeneic HCT maintenance therapy needs to be explored in the context of well-designed prospective trials; and (4) Prospective randomized trials need to be performed to define the role salvage allogeneic HCT in patients with MM relapsing after primary therapy.

Keywords: Myeloma; Salvage therapy; Stem cell transplantation.

Figure 1

(A) Number or salvage HCT performed for MM in North America over time (CIBMTR registry). (B) Type of salvage HCT performed for MM over time (CIBMTR registry).

Figure 2

(A) Since 1995, evolution of salvage treatment after autologous transplantation in Europe: no transplantation versus autologous transplantation. 2014 data is incomplete (EBMT registry). (B) Since 1995, evolution of salvage autologous transplantation in Europe: single (AUTO1) versus double (AUTO2) versus tandem autoallo (ALLO2). 2014 data is incomplete (EBMT registry).

Figure 3

(A) Expert consensus on role of autologous HCT as consolidation therapy of an initial remission after first autograft of greater than 24 months (0 strongly agree and 10 strongly disagree, ordinate axis is the number of people who voted). (B) Expert consensus on role of autologous HCT as consolidation therapy of an initial remission after first autograft of less than 6 months (0 strongly agree and 10 strongly disagree, ordinate axis is the number of people who voted). (C) Expert consensus on role of autologous HCT as consolidation therapy of an initial remission after first autograft of between 12 and 24 months (0 strongly agree and 10 strongly disagree, ordinate axis is the number of people who voted).

Figure 4

(A) Expert consensus on role of allogeneic HCT as consolidation therapy of an initial remission after first autograft of greater than 24 months (0 strongly agree and 10 strongly disagree, ordinate axis is the number of people who voted). (B). Expert consensus on role of allogeneic HCT as consolidation therapy of an initial remission after first autograft between 12 and 24 months (0 strongly agree and 10 strongly disagree, ordinate axis is the number of people who voted). (C) Expert consensus on role of allogeneic HCT as consolidation therapy of an initial remission after first autograft of less than 6 months (0 strongly agree and 10 strongly disagree, ordinate axis is the number of people who voted).