MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple myeloma patients

Abstract

Minimal residual disease (MRD) testing is increasingly important for the assessment of treatment response in patients diagnosed with multiple myeloma. In fact, MRD negativity is consistently associated with a better PFS and overall survival. [1][2][3][4][5][6][7][8][9] In this issue of the Journal, Sherrod et al. 10 publish a timely review article focusing on MRD testing after stem cell transplantation for patients with multiple myeloma. They review and discuss novel biochemical assays (including serum-free light-chain assays and heavy-chain/light-chain assays) as well as novel methods to measure MRD, including multi-parametric flow cytometry, PCR, next-generation sequencing and functional imaging modalities. They outline the main literature on this topic and highlight on the strengths and weaknesses of each of these assays and approaches. Furthermore, they address practical questions related to MRD testing after stem cell transplantation for patients with multiple myeloma. As part of their conclusion, they point out the clear need for International Myeloma Working Group response criteria to be revised and updated to include MRD.In the final part of their paper, Sherrod et al. 10 conclude that the treatment paradigm for multiple myeloma continues to evolve, and as the depth and duration of responses continue to improve, more sensitive measures of disease evaluation should be integrated into the response algorithm. As MRD research continues to develop, in their opinion, two clinical areas will be of particular interest with regard to the use of high-dose melphalan (HDM) therapy followed by autologous stem cell transplant (ASCT) in multiple myeloma.The first interest area involves the question of whether it is beneficial for multiple myeloma patients to move forward with upfront HDM-ASCT or if a delayed HDM-ASCT following a set number of therapeutic cycles is equally good or better. As pointed out by Sherrod et al. 10 the role of upfront versus delayed HDM-ASCT is being evaluated in the ongoing Intergroupe Francophone du Myélome (IFM)-Dana-Farber Cancer Institute (DCMI) study (NCT01208662), in which patient receive three cycles of RVd (lenalidomide, bortezomib and dexamethasone) combination therapy followed by upfront HDM-ASCT, followed by two additional cycles of RVd and lenalidomide maintenance versus an additional five cycles of RVd and lenalidomide maintenance with the option of a delayed HDM-ASCT at relapse. The duration of lenalidomide maintenance is restricted to 1 year in the IFM part of the study, whereas the DFCI part of the study uses lenalidomide maintenance until disease progression. At the 2015 American Society of Hematology (ASH) meeting in Orlando, Attal 11 presented the results from the IFM part of the study, showing that the average PFS was longer in the arm with three cycles of RVd combination therapy followed by upfront HDM-ASCT, followed by two additional cycles of RVd and 1 year of lenalidomide maintenance. In the upfront HDM-ASCT arm, 93% of patients underwent ASCT and five toxic deaths occu...

Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes

“…Adapted from Landgren et al . . HDM ‐ ASCT , high‐dose melphalan and autologous stem cell transplantation; MRD , minimal residual disease.…”

New Developments in Diagnosis, Prognosis, and Assessment of Response in Multiple Myeloma

“…At the beginning of the 21 st Century, multiple myeloma had an average overall survival of about 3 years (4). Around that time, 3 drugs (bortezomib, lenalidomide, and thalidomide) were introduced for the treatment of multiple myeloma and, in 2012, carfilzomib received accelerated approved by the U.S. Food and Drug Administration (FDA).…”

“…In parallel with these practical steps, we need to continue developing better MRD tests with higher sensitivity and also MRD tests that ultimately can be based on peripheral blood instead of bone marrow aspirates. In our opinion, access to future blood-based MRD tests will have the potential to transform the myeloma field and open up avenues for response-driven treatment strategies with the aim to tailor treatment, for maximal efficacy and limited toxicity (4). In the future, it is possible that many patients will live with multiple myeloma inactive for a very long time and that treatment adjustments will be based on changes in biomarkers before the patient develops any symptoms (functional cure).…”

“…Reprinted from ref. 4. *A lower hazard ratio indicates decreased risk for each survival endpoint (i.e.…”

“…In parallel with the strong drug pipeline, clinical management of multiple myeloma has changed drastically the past few years. Without any doubt, the use of modern combination therapy integrated with modern clinical management will continue to deliver substantially longer overall survival for patients with multiple myeloma in years to come (4). …”