Paul G. Richardson, MD, On Using MRD to Inform Choice Between Systemic Therapy and Transplant in Newly Diagnosed Myeloma

Paul G. Richardson, MD, looks at MRD data from the DETERMINATION study for its potential to guide treatment selection in newly diagnosed multiple myeloma.

At the 2022 American Society of Clinical Oncology Annual Meeting, Paul G. Richardson, MD, clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute as well as RJ Corman Professor of Medicine at Harvard Medical School, both in Boston, Massachusetts, spoke with CancerNetwork® about minimal residual disease (MRD) data from the phase 3 DETERMINATION trial (NCT01208662) and how these results may help inform care of patients with newly diagnosed multiple myeloma. In the trial, efficacy of lenalidomide, bortezomib, and dexamethasone (RVd) followed by continuous lenalidomide (Revlimid) maintenance and delayed autologous stem cell transplant (ASCT) was compared with immediate ASCT.


One of the most exciting aspects of the trial was MRD [minimal residual disease] testing. We did testing using next-generation sequencing with a sensitivity of 10–5, and we were able to show with our preliminary analysis in the first 100 patients per arm that about 40% achieved MRD negativity with RVd alone, which was encouraging. Remarkably with early transplant, that number improved to around 52%. The numbers are such that we can’t declare statistical significance on that analysis, but it’s an encouraging trend. What is so important though is that once a patient achieved MRD negativity, our preliminary analysis suggested it was remarkably stable for progression-free survival. If you achieve MRD negativity, progression-free survival, regardless of which treatment you have, is good. That [helps us guide our patients]. They can keep transplants in reserve if they achieve a high-quality response with MRD negativity. That’s a justifiable thing to do. Conversely, if they are MRD positive, the response is not great, and the disease is behaving badly, that might be the setting in which high-dose melphalan with stem cell support matters.


Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): The phase 3 DETERMINATION trial. J Clin Oncol. 2022;40(suppl 17):LBA4. doi:10.1200/JCO.2022.40.17_suppl.LBA4