Expert perspective on results from the MASTER study analyzing daratumumab in combination with KRd in transplant-eligible newly diagnosed multiple myeloma.
Saad Z. Usmani, MD: Another very interesting study that was presented at ASH [American Society of Hematology annual meeting] was the final analysis of the MASTER trial. MASTER was a response adaptive single-arm phase 2 study that was conducted by Luciano Costa, [MD, PhD]. Patients were enrolled from different institutions, so it was a multi-institutional single-arm study. What was unique about the study was the schema of having sustained MRD [minimal residual disease] to guide the decision of whether to stop treatment for any given patient. The induction regimen was daratumumab with carfilzomib, lenalidomide, and dexamethasone, so daratumumab-KRd was utilized, for 4 cycles. Then all the patients had MRD testing by NGS [next-generation sequencing], then patients went on to receive autologous stem cell transplant. Post-transplant, they had MRD testing as well.
If they were MRD negative at both of those points, they were termed MRD-SURE [treatment-free observation and MRD surveillance], and they were observed without any further treatment. If they were MRD positive, they went on to have 4 cycles of daratumumab-KRd as consolidation. This was followed by another MRD test. If patients had 2 consecutive MRD negative tests, then they were called MRD-SURE. Again, treatment-free observation was utilized. If they still had not achieved that goal, another 4 cycles of consolidation were given. If at that point patients were MRD negative at 2 consecutive points, then they would be undergoing surveillance without any treatment, otherwise, they were placed on lenalidomide maintenance.
There were several steps, 3 specific steps, where patients were allowed to discontinue treatment and be observed with MRD surveillance. The results that Dr Costa presented were quite interesting, specifically in the context of whether patients had high-risk cytogenetics, either a single feature or 2 or more features. He presented data on how many patients were achieving MRD negativity at both 10-5 and 10-6 at any given time based on this therapeutic schema. What he’d shown was that even though the MRD negativity at 10-5 was similar across these different groups, the 10-6 MRD negativity was actually lower for patients who had 2 or more high-risk features compared to those who did not. This actually translated into a difference in PFS [progression-free survival] as well as overall survival for that group of patients.
This is a very important point to make. I think perhaps the most important point from this really nice hypothesis-generating study is that achieving MRD negativity at 10-6 or higher may be the right exploratory end point, or potentially surrogate end point, for the high-risk patients who have 2 or more high-risk features. What will come out of this MASTER protocol, I think this helps us establish an important guiding post for future randomized studies that can test this hypothesis compared to a standard of care treatment approach for patients with myeloma.
Transcripts edited for clarity.