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 nee...

Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party

“…The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN), the American Society of Blood and Marrow Transplantation (ASBMT) and the European Society of Blood and Marrow Transplantation (EBMT) reported consensus on salvage options in patients with relapsed MM. 12 The authors recommended that allogeneic HSCT should be considered as an appropriate therapy for any eligible patient with early relapse (<24 months) after primary therapy that included an autologous HSCT and/or high-risk features.…”

“…Allogeneic HSCT (allo-HSCT) remains a potentially curative treatment but its use is still controversial because of its high morbidity and mortality. 9,10,11,12,13,14 Conventional myeloablative conditioning (MAC) regimens have given way in the last decade to reduced intensity conditioning (RIC) regimen that has been more frequently used in the last decade due to significantly reduced transplant-related mortality, which has decreased to 10-20% but was associated with high relapse rates compared with MAC. 15,16 The most important predictors of outcome are the low-tumor burden at the time of transplant and the management of chronic graft-versus-host disease (GvHD) after transplantation.…”

Management of high-risk Myeloma: an evidence-based review of treatment strategies

“…While the PFS was significantly longer in the donor compared to the no-donor group (2-year PFS 42% vs 18%), OS was equivalent (2-year OS 54% vs 53%) [116]. Therefore, although alloSCT can be considered an option in patients relapsing early after upfront autoSCT, this should only be in the setting of well-designed clinical trials [112].…”

“…While salvage autoSCT in the relapsed setting has been shown to be feasible and effective, most studies see an inferior outcome for patients with shorter PFS after initial autoSCT [110,111] and the consensus conference of the IMWG and the American and European Blood and Marrow Transplantation Societies only recommends a salvage ASCT as standard-of-care in patients with a remission after initial autoSCT of greater than 18 months [112]. In a recent retrospective study comparing second autoSCT to non-SCT novel agent-based regimens in the relapsed setting, a second autoSCT was associated with a significantly longer OS and time-to-next-treatment compared to the non-SCT strategies.…”

Hematopoietic Stem Cell Transplantation: A Bioethical Lens

“…In turn, this has also led to the production of specific guidelines (e.g., on fertility preservation and donor algorithm selection) [3–6]. …”