In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P ‫؍‬ .004) or with VBMCP/ VBAD/B (46% vs 38%, P ‫؍‬ .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher preand posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no.

Despite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM. Daratumumab, targeting CD38, has multiple mechanisms of action including modulation of the immunosuppressive bone marrow micro-environment. In addition to the remarkable single agent activity in refractory MM, daratumumab produced deep responses and superior PFS in MM when combined with lenalidomide/dexamethasone, or bortezomib/dexamethasone. Other anti-CD38 antibodies, such as isatuximab and MOR202, are undergoing assessment. Elotuzumab, targeting SLAMF7, yielded superior response rates and PFS when combined with lenalidomide/dexamethasone. New combinations of these next generation novel agents and/or antibodies are undergoing clinical trials. Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone. Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. Pembrolizumab, an anti-PD1 check-point inhibitor, is being tested in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone. Chimeric antigen receptor-T cells targeting B-cell maturation antigen have yielded deep responses in RRMM. Finally, salvage autologous stem cell transplantation (ASCT) remains an important treatment in MM relapsing/progressing after a first ASCT. Herein, the clinical trial data of these agents are summarized, cautious interpretation of RCTs highlighted, and algorithm for salvage treatment of relapse/refractory MM proposed.

ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.

IntroductionTreatment of patients with multiple myeloma (MM) is disappointing. In this regard, the Southwest Oncology Group (SWOG) experience on standard dose therapy in 7 consecutive, large phase 3 studies has shown median survival times of less than 3 years, irrespective of the treatment given. 1 In addition, the Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA) group found that increased doses of conventional chemotherapy did not result in significant prolongation of survival. 2 Finally, meta-analysis of 6633 patients from 27 randomized trials failed to show any superiority of combination chemotherapy over melphalan/ prednisone in terms of duration of response and survival. 3 Furthermore, the Nordic Myeloma Study Group reported no survival improvement in conventionally treated younger patients with myeloma in the past 2 decades. 4 These limitations led to the current tendency to offer high-dose therapy (HDT)/stem cell support to MM patients as part of the frontline treatment. 5 Two randomized trials conducted by the Intergroup Français du Myeloma (IFM) and the Medical Research Council (MRC) showed that HDT significantly increased complete remission (CR), event-free survival (EFS), and overall survival (OS) compared with conventional chemotherapy. 5,6 However, 2 other randomized trials, reported in abstract form, failed to show any superiority of autologous J.B. and J.S.M. created the initial concept/design of the trial, analyzed and interpreted the data, wrote the manuscript, modified subsequent drafts, and finalized the manuscript; L.R. and A. Sureda contributed to analysis and interpretation of the data and to drafting the manuscript; J.B., J.S.M., L.R., and A. Sureda brought a significant number of patients to the study; M.F. participated in the analysis of the data and in the updating process throughout the study period; and J.M.R., J.D.-M., J.G.-L., M.V.M., L.P., J.F.-C, J.M.M., P.G., F.C., M.C., J.T., S.G., M.J.M., A.B., A. Soler, and L.F. participated in the conception/design of the study, included patients, provided the PETHEMA database with the patient data and periodic updating, and actively discussed the progress of the trial at the annual PETHEMA meetings. All the authors are members of PETHEMA and reviewed and approval the final version of the manuscript.An Inside Blood analysis of this article appears in the front of this issue.Reprints: Joan Bladé , Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain; e-mail: jblade@clinic.ub.es.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S.C. section 1734. For personal use only. on March 22, 2019. by guest www.bloodjournal.org From transplantation. 7,8 The objective of the present study was to investigate, in a prospective randomized trial, the efficacy of HDT intensification therapy compared with continuation with conventional chemotherapy in patients wit...