Institution: Sylvester Comprehensive Cancer Center ASCO 2025 | An update on the ADVANCE trial comparing Dara-KRd versus KRd in newly diagnosed myeloma

At ASCO 2025, I had the honor to present for the very first time the ADVANCE randomized clinical trial, which is an investigator-initiated study for newly diagnosed multiple myeloma patients. It’s a large multi-center study. The primary endpoint for the study was minimal residual disease negativity, 10 to minus 5, in the intention to treat population after eight cycles of combination therapy. And the study compared carfilzomib-lenalidomide-dexamethasone plus daratumumab to carfilzomib-lenalidomide and dexamethasone. And the study showed a highly significantly better MRD negativity rate in the DARA-KRd arm. The odds ratio was 2.9 and the p-value was less than 0.0001. So it was about 60% MRD negativity in the Dara-KRd arm. The follow-up was, the median follow-up was 31.2 months, so almost three years. And the results are very impressive for the Dara-KRd regimen. And at almost three years of follow-up, 92% of the patients remain free from progression. So this is a very, very effective therapy. 

I also highlighted on the safety data, and we concluded that there is really no new safety signal. The signal we see is same as we have seen for the individual drugs in the past. It was very balanced between the two arms. 

I also highlighted that a big result from this study is actually that we were able to enroll 306 patients at only seven academic centers here in the United States. Many times we see that the trials are done in hundreds of sites. Many of the cooperative group studies have enrolled one or two patients per site. But we have seven dedicated independent academic centers. This was University of Miami, Sylvester Comprehensive Cancer Center. We were the lead site, but we also had Memorial Sloan Kettering, MD Anderson, Moffitt Cancer Center, Roswell Park, Stony Brook in New York, and Huntsman Cancer Center in Utah. So these seven groups together were able to enroll 306 patients in a randomized, newly diagnosed multiple myeloma study that’s investigator initiated. So that’s a quite impressive result by itself. 

I highlighted lastly that the future directions for this study will be to further dissect and understand underlying mechanisms of achieving and sustaining MRD negativity. Why do some patients achieve MRD negativity and sustain it? And there are some patients where this doesn’t happen. Also understanding the interaction between the disease biology, the host immune status, and the different drugs, plus and minus transplantation. So the study has a lot of correlative science, and it’s a multi-omic study. And I also ended my talk saying that we are just about to open the ADVANCE 2.0 study that builds on the ADVANCE study. So that new study will include a BCMA/CD3 bispecific antibody, elranatamab, plus KRd or Rd. And that is going to open in June of 2025.

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