Dara-KRd in Transplant-Eligible Multiple Myeloma

At the American Society of Hematology (ASH) annual meeting, researchers presented results of the phase II MASTER trial in newly diagnosed multiple myeloma.

In this video, courtesy of the Video Journal of Hematological Oncology (VJHemOnc), Luciano Costa, MD, PhD, of the University of Alabama at Birmingham School of Medicine, discusses the findings from the trial, which investigated daratumumab (Darzalex), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone — the Dara-KRd regimen — followed by autologous transplantation.

Following is a transcript of his remarks:

So at this 63rd ASH, we presented the final primary endpoint analysis of the MASTER trial. This was a study where we enrolled patients with newly diagnosed multiple myeloma who are amenable to autologous transplantation. And we treated everybody with four cycles of Dara-KRd followed by an autologous transplant, and followed by MRD [minimal residual disease] response-adapted consolidation that could be zero, four, or eight additional cycles of Dara-KRd.

We measured MRD by next-generation sequencing clonoSEQ at each of those blocks of therapy, and for patients who had two consecutive MRD reads below 10^-5 — for example post-induction and post-transplant, or post-transplant and post four cycles of consolidation — those patients ceased therapy and entered a phase that we called MRD-SURE, where they are observed without any treatment but they are surveilled for the resurgence of MRD or clinical relapse.

And what we found is, in this population with 123 patients with enrichment for patients with high-risk cytogenetics, we found that the regimen was highly effective, at 98% overall response rate, including 88% of complete responses, but more important that 80% of the patients achieve MRD negative to 10^-5 and 66% MRD negative to 10^-6. Importantly, 71% of the patients were able to reach two MRD negative reads and cease therapy, and are being observed.

With that treatment, 2-year progression-free survival remains above 95% for patients with standard-risk myeloma or with high-risk with one chromosome abnormality. But it’s lower for patients with two or more high-risk abnormalities that we call ultra high-risk myeloma. The same thing about overall survival.

If you take those patients who cease therapy because they had two MRD negatives and are being observed, after 1 year the risk of resurgence of MRD is below 5% for standard- and high-risk, but it’s higher at 27% for patients with ultra high-risk myeloma.

What we learned from this study is first, that we can do real-time response adapted therapy trials in myeloma with it applicable to 96% of the patients, and you are able to act on those MRD results. And, there is this really clearly delineated path for treatment de-escalation, treatment cessation for patients for the vast majority of the patients, including some high-risk patients. But for those in the minority that have ultra high-risk myeloma, particularly if they fail to reach very deep response, there’s still the ongoing necessity to further improve the therapy, which we intend to pursue going forward.