Minimal residual disease testing after stem cell transplantation for multiple myeloma

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

“…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.…”

“…As stated by Sherrod et al 10 the answers to these future questions are of particular interest in the United States, since increasing numbers of patients will become MRD 10 − 6 negative after having received modern therapies that are readily available through Food and Drug Administration approval. Overall, MRD testing in multiple myeloma care has the potential to better assess response to treatment, to risk stratify patients on clinical trials and to be integrated in treatment decisions in the standard of care setting.…”

“…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.…”

“…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.…”

“…As opposed to a fixed number of RVd cycles, Sherrod et al 10 discuss that the actual MRD status could potentially be used to identify patients who benefit from upfront ASCT as a response-deepening strategy. As proposed by Sherrod et al 10 a modern study design would be to randomize patients who achieve MRD 10 − 6 negative status to upfront HDM-ASCT versus delayed HDM-ASCT; in parallel, patients who do not achieve MRD 10 − 6 negativity after a defined number of combination cycles (for example, six) could be randomized to various treatment strategies, such as immediate HDM-ASCT versus further cycles of induction until the achievement of MRD 10 − 6 followed by re-randomization to HDM-ASCT, or not. In our opinion, an MRD-driven study-built on modern combination therapy (such as carfilzomib, lenalidomide and dexamethasone) 8 -is a logical next step from where we are right now (Figure 1).…”