Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study

Abstract

Key Points• Tandem autologous/reducedintensity allogeneic transplantation is superior to autologous transplantation alone in multiple myeloma.Long-term follow-up of prospective studies comparing allogeneic transplantation to autologous transplantation in multiple myeloma is few and controversial. This is an update at a median follow-up of 96 months of the European Group for Blood and Marrow Transplantation Non-Myeloablative Allogeneic stem cell transplantation in Multiple Myeloma (NMAM)2000 study that prospectively compares tandem autologous/reduced intensity conditioning allogeneic transplantation (auto/RICallo) to autologous transplantation alone (auto). There are 357 myeloma patients up to age 69 years enrolled. Patients with an HLA-identical sibling were allocated to auto/RICallo (n 5 108) and those without to auto alone (n 5 249). At 96 months progression-free survival (PFS) and overall survival (OS) were 22% and 49% vs 12% (P 5 .027) and 36% (P 5 .030) with auto/RICallo and auto respectively. The corresponding relapse/progression rate (RL) was 60% vs 82% (P 5 .0002). Non-relapse mortality at 36 months was 13% vs 3% (P 5 .0004). In patients with the del(13) abnormality corresponding PFS and OS were 21% and 47% vs 5% (P 5 .026), and 31% (P 5 .154). Long-term outcome in patients with multiple myeloma was better with auto/RICallo as compared with auto only and the auto/RICallo approach seemed to overcome the poor prognostic impact of del(13) observed after autologous transplantation. Follow up longer than 5 years is necessary for correct interpretation of the value of auto/RICallo in multiple myeloma. (Blood. 2013;121(25):5055-5063) Introduction Despite improvements in survival of patients with multiple myeloma by treatment with new drugs such as thalidomide, bortezomib, and lenalidomide, documented cures of the disease are lacking. Allogeneic hematopoietic stem cell transplantation has been studied, but results have been controversial. [1][2][3][4][5][6][7] Recently, we published the first results of a prospective Non-Myeloablative Allogeneic stem cell transplantation in Multiple Myeloma study (NMAM2000) comparing tandem autologous (auto)/reduced intensity conditioning allogeneic transplantation (RICallo) with autologous transplantation-single (auto) or tandem(auto/auto).8 Although superior progression-free survival (PFS), overall survival (OS), and relapse rate (RL) using the tandem auto/RICallo treatment modality was documented using appropriate tests for crossing curves, interpretation of the results has been controversial. This update of the study, after a median follow-up of 96 months, supports and strengthens the previous conclusion that the tandem auto/RICallo approach prolongs PFS and OS long term due to lower progression/relapse rate. This is true both using an intention to treat analysis and an analysis that compares only those patients who received treatment according to protocol. Considering this study started in the era predating "novel" agents, our results suggest that reports of the "death" ...

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation

“…3 Over the last decade, a number of studies investigated up-front reduced intensity-conditioned (RIC) allo-SCT and reported substantially lower NRM rates compared with MA allo-SCT. [4][5][6][7][8][9][10][11][12][13] Whereas some of these studies reported better longterm outcomes with RIC allo-SCT compared with tandem autologous hematopoietic SCT (auto-SCT), others failed to demonstrate a benefit of up-front RIC allo-SCT. Therefore, there is widespread reluctance to offer patients' up-front allo-SCT, which is at least partly due to prolonged remissions that can be achieved following induction and/or maintenance therapy with novel agents.…”

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…84 In the EBMT-NMAM 2000 study, at a median follow-up of 96 months, 21% of patients with the higher-risk deletion 13 abnormality by FISH receiving tandem ASCT-allo-SCT were progression free compared with 5% in the tandem ASCT group. 35 However, there was no survival benefit in this group in BMT CTN 0102 33 when compared with tandem ASCT. A single center study has shown similar survival in the high-risk group compared with the standard-risk group; 37 this suggests that allo-SCT may overcome the negative impact of high-risk disease.…”

“…With a median follow-up of 8 years, the PFS and OS for the tandem ASCT-allo-SCT was superior to the tandem ASCT group; PFS was 22% vs 12% (P = 0.027), and the OS was 49% vs 36% (P = 0.030), respectively, favoring tandem ASCT-allo-SCT. 34,35 Relapse was lower in the allo-SCT cohort (60% vs 82%, P = 0.0002), although TRM was 12% in this cohort vs 3% in the ASCT cohort. In patients with the high-risk deletion, 13 chromosome abnormality by FISH, PFS and OS favored the allo-SCT cohort-21% vs 5%, P = 0.026 and 47% vs 31% (P = 0.154), respectively.…”

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

“…Moreover, the use of allo-SCT in MM also represents a certain risk of GvHD and transplantrelated mortality, despite the use of RIC regimens. Several studies, including phase III multicenter studies, compared auto-SCT followed by RIC allo-SCT (auto-allo-SCT) to a tandem auto-SCT approach [70,[72][73][74][75][76][77][78]. Auto-allo-SCT was not superior to tandem auto-SCT in patients with high-risk de novo MM [72] or in patients with standard-risk disease [70].…”

“…Another study showed, in contrast, an overall benefit for auto-allo-SCT arm in newly diagnosed MM with superior survival [73]. Moreover, long-term outcome was better in patients that received auto-allo-SCT rather than tandem auto-SCT [75,77]. Finally, in patients that relapsed after the first auto-SCT, controversial results have been shown regarding the feasibility of allo-SCT as salvage therapy compared to auto-SCT [76,78].…”