SummaryBortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1AE3 mg/m 2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1-4, 8-11 and 15-18 during cycle 1 and days 1-4 during cycles 2-4. During days 1-4, patients also received 0, 4AE5 or 9 mg/m 2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.

In patients with previously untreated multiple myeloma, long-term outcome with respect to progression-free survival, overall survival, and relapse rate is superior after auto-allo compared with auto only. Nonrelapse mortality is at a reasonable level in both groups.

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" ...

VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.