Randomized phase III trial of consolidation therapy with bortezomib–lenalidomide–Dexamethasone (VRd) vs bortezomib–dexamethasone (Vd) for patients with multiple myeloma who have completed a dexamethasone based induction regimen

Long-awaited results from the the Southwest Oncology Group (SWOG) trial comparing bortezomib–lenalidomide-dexamethasone (VRd) versus lenalidomide-dexamethasone (Rd) as induction treatment for previously untreated multiple myeloma (MM) patients were recently presented (S0777).1 Results justified the early adoption of VRd in the frontline setting over 5 years ago by the NCCN based on Level 2A evidence according to their guidelines.2 The randomized study E1A05 also sought to evaluate VRd superiority over a doublet (Vd), but in the consolidation setting. The trial was closed to enrollment prematurely due to slow accrual. Results reported here include 48 enrolled patients.This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L Comis, MD, and Mitchell D Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under award numbers: CA180820, CA180794, CA21115, CA23318, CA66636, CA180790, CA13650, CA189956, CA35412, CA15488, CA180799 and CA21076.http://www.sherpa.ac.uk/romeo/issn/2044-5385/am2016Medical Oncolog

International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with tAML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy