CancerNetwork® sat down with Luciano Costa, MD, PhD, at the 2021 International Myeloma Workshop to discuss key implications from the phase 2 MASTER trial, utilizing daratumumab, carfilzomib, lenalidomide, and dexamethasone.
At the 2021 International Myeloma Workshop, CancerNetwork® spoke with Luciano Costa, MD, PhD, of O’Neal Comprehensive Cancer Center, about the implications of the phase 2 MASTER trial (NCT03224507) with daratumumab (Darzalex), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Dara-KRd) in patients with newly diagnosed multiple myeloma. Additionally, Costa also discusses questions left by the study that future research efforts may answer.
This is a single arm phase 2 trial, so it's hard to say that this is going to be practice changing tomorrow. I think that is a steppingstone for several future developments, in my opinion. One of them is to prove that you can do [minimal residual disease] (MRD) response-adaptive therapy in a multi-institutional setting. Almost the totality of MRD data from clinical trials comes from collecting samples and analyzing them in batches and not using that MRD data in real time to adjudicate therapy; that was not the case here, but that could be done. We had 99% compliance in obtaining those samples. I think it is a small thing, but is not to be forgotten; it is very important.
The second is, we've seen that the vast majority of patients do achieve that deep level response. We had two-thirds of patients reach MRD 10-6. That's really a testament to the efficacy of the regimens that we currently have. But on the other side, we also saw 6 patients progress while on therapy. Those are people who had an initial response, and then their myeloma got worse, even though there was still room for drug therapy they never had a break. We should look at those patients who are the majority, who do very well, and have deep responses with the modern therapies that we have, and really start looking at the escalation of therapy. I’m not sure all those patients need a transplant and I’m sure other patients need indefinite maintenance.
Those questions should be answered in that population of early deep responders on a prospective matter. But conversely, we still have a subset of ultra-high-risk patients who still do poorly, even though you're giving maximum therapy. I think those patients need an early introduction of novel agents. I think we need to explore in high-risk patients and particularly ones now reaching MRD negativity and the possibility of early deployment of novel agents, such as CAR T-cell [therapy] or bi-specific T-cell engagers. That should be done also in a prospective manner.
Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd), autologous transplantation and MRD response-adapted treatment duration and cessation in newly diagnosed multiple myeloma (NDMM). Paper presented at: 18th International Myeloma Workshop; September 8-11, 2021; Vienna, Austria. Accessed September 11, 2021.