Summary of the 2019 Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling

Abstract

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup has organized an annual workshop focused on minimal residual disease (MRD) testing and immune profiling (IP) in multiple myeloma since 2016. In 2019, the workshop took place as an American Society of Hematology (ASH) Friday Scientific Workshop titled "Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma." This workshop focused on 4 main topics: the molecular and immunologic evolution of plasma cell disorders, development of new laboratory-and imaging-based MRD assessment approaches, chimeric antigen receptor T cell therapy research, and statistical and regulatory issues associated with novel clinical endpoints. In this report, we provide a summary of the workshop and discuss future directions.

MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials

“…According to our results, for patients who do not achieve MRD − status or who convert from MRD − to MRD + status, it should be noted that although prolonged therapy significantly improved PFS, the benefit was limited to certain cases (potentially those converting from MRD + to MRD − ). Therefore, the role of MRD in treatment decisions remains to be established and is being investigated in ongoing randomized studies evaluating MRD-directed therapy 31 ). Importantly, our results highlight that MRD-directed therapy should rely on MRD dynamics rather than MRD status assessed at a single time point.…”

Future Directions in Maintenance Therapy in Multiple Myeloma

“…However, a number of issues must be resolved for MRD to gain designation as a surrogate endpoint from a regulatory perspective, including the optimal MRD assessment methodology, sensitivity of assay, timing of assessments, duration of sustained MRD negativity, and the incorporation of disease assessment outside of the bone marrow (i.e., with advanced imaging) [ 51 ]. There is an ongoing collaboration between academia and industry representatives (International Independent Team for Endpoint Approval of Myeloma MRD (i 2 TEAMM)) that is attempting to establish an MRD-based endpoint as a surrogate for PFS [ 52 ].…”