Luciano Costa, MD, PhD, Discusses Topline Data Utilizing KRd in Newly Diagnosed Myeloma

At the 2021 International Myeloma Workshop (IMW), CancerNetwork® spoke with Luciano Costa, MD, PhD, Associate Director for Clinical Research at O’Neal Comprehensive Cancer Center, about key findings from the phase 2 MASTER trial (NCT03224507), which examined the use of daratumumab (Darzalex), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Dara-KRd) in patients with multiple myeloma.

Transcript:

The update that we provided at IMW was the primary outcome analysis, which was the proportion of patients who reached minimal residual disease [MRD]–negativity at 10-5 , [which was] was 80%, across all comers. That was a population that was in reach to have a higher proportion of patients with high-risk disease. Twenty percent of the patients were considered ultra-high risk for having 2 or more high-risk cytogenetic abnormalities.

We also learned several other lessons from this study. One is that this regimen with dara-KRd is well tolerated and leads to very quick responses in nearly all patients, who had the objective response after 2 cycles in close to 90% of the patients who had a [very good partial response] before transplant. We also learned or confirmed that even though we are using quadruple very active therapy, for majority of patients, we still see a deepening of response with autologous transplant that can be seen both by the higher proportion of patients being MRD negative after transplant. On an individual level, since you can track the burden of MRD, you can see a lowering of that burden with autologous transplant. We also [saw] something very interesting that when you look at 10-5, the proportion of patients reaching MRD negativity [did not] seem to be affected by whether those patients are standard, high, or ultra-high risk. Up to 10-6, it becomes a little bit different and patients with ultra-high-risk disease are less likely to achieve that level of response. We look forward to longer follow up to understand how this different risk profile affects the likelihood of those patients losing MRD negative response; in other words, having resurgence of MRD or progression.

Reference

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.