MILESTONE Trial: MRD Adapted Deferral of Transplant in Dysproteinemia | Susan Bal, MD | IMS 2024

Hi, I'm Susan Baal at the University of Alabama at Birmingham, and I was delighted to share the first results from an investigator-initiated phase two trial of measurable residual disease or MRD-adapted deferral of transplant in dysprotinemia, also known as the milestone clinical trial. So this is a small pilot feasibility study, essentially trying to understand what we can use MRD that we obtained following induction treatment for newly diagnosed multiple myeloma patients and use that MRD result to make the decision about whether or not we should proceed with transplant. So the primary endpoint of our study was to understand if we can use MRD as a strategy to make transplant decisions. So what we did is we included 20 patients, about 50% of our patients were male, 50% of those were over the ages of 70. We had about 15% high risk and up to 40% if you add a gain of 1q, and we had up to 45% racial and ethnic minorities. So this was a very diverse population. What we saw was very impressive results in terms of the initial MRD response following induction was 25%, and all of those patients per protocol were able to defer a transplant. Following their consolidation therapy, we saw that the MRD responses increased to 55%, and then the best response overall in terms of MRD on the entire study was 65%. So using a quadruplet standard combination of DERA-VRD for induction for six cycles, we were able to allow a quarter of our patients to defer transplant knowing that they had had a deep enough response even if they were good candidates. All of those patients did proceed with stem cell collection, so in the future they still have the option of going through transplant, but what we are showing is with the best MRD response with a two-year follow-up of 65%, that you can have equivalent outcomes as receiving a quadruplet and transplant and then still defer it and have similar outcomes, which is huge for our patients because transplant has so many toxicities such as, you know, mucusitis, difficulty eating, weight loss, hair loss, low blood count, staying in the hospital for a period of time, risk of infections, and then longer term side effects such as a proportion of patients will have a higher risk of hematologic cancers that can occur in the later period. So, you know, it's really not something that most of our patients want to go through, but occasionally they feel compelled because of the increased depth and duration of response, but now with this MRD adapted strategy, we for the first time have an opportunity to make an informed decision with our patients about the risk and benefit ratio. Now, of course, you know, we'll have to see if the longer term follow-up outcomes are similar, but this is now being tested in the context of two large randomized clinical trials, the ongoing MIDAS trial whose results we'll hear at this meeting, as well as the Master II trial that is now open at UAB. So, this also helped us understand whether the Master II trial would be feasible in many ways and see if six cycles of induction therapy would still lead to adequate stem cell output as well as help us make a real-time decision using MRD.