Facon, Thierry T.F.

Key Points Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma. Patients achieving complete or very good partial response with Rd benefited greatly from continuous vs fixed treatment in terms of PFS.

Key Points Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile in patients with relapsed/refractory MM. Venetoclax monotherapy has demonstrated antimyeloma activity in patients with relapsed/refractory MM positive for t(11;14).

Key Points In relapsed/refractory MM, venetoclax plus bortezomib and dexamethasone appears to be safe and efficacious. This is a novel therapeutic approach for MM.

Key Points Elderly patients with myeloma are heterogeneous and assessment strategies are needed to define the frailty profile. The proposed frailty score aims to better assess patients and provide them with more suitable therapies.

Abstract Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established.

Abstract It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma, detailed definitions for patient populations, lines of therapy, and specific endpoints. We propose that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript.

Abstract Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib versus high-dose dexamethasone. In this updated analysis (median follow-up: 22 months), survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall and complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230).