EHA 2025 | Updates from the MIDAS study: MRD-guided therapy following IsaKRD in newly diagnosed myeloma

Well, as we’ve heard, there’s been some beautiful presentations, both at ASCO and at EHA, of what I think is one of the most important current upfront transplant studies being performed led by our colleagues in the IFM under the principal leadership of Dr Aurore Perrot. And she and her colleagues have shown really remarkable results for what I think is a very important and novel approach where essentially a quadruplet of drugs has been used for induction remission therapy, KRD-isatuximab. She and her team have reported that there are remarkably high response rates with this approach. There’s very favorable treatment-related toxicity profile, recognizing that carfilzomib can carry with it some issues. But that being said, the response data are superb and the MRD rates are remarkably high. 

And what Aurore has just presented at ASCO and her colleague Cyrille here at EHA, and is actually now published in the New England Journal, is the results in terms of the primary endpoint, which were the conversion of MRD rates across transplant in the standard risk patients who are MRD negative versus not, and in the high-risk MRD positive patients where single transplant was compared to tandem transplant. 

And the remarkable results really were that MRD did not meaningfully change with the use of either single transplant in the standard risk MRD negative randomization, and also surprisingly did not meaningfully change either in the second transplant group of the high-risk MRD-positive study group patients. So to interpret that, it just simply suggest that the improvement in MRD for the use of high-dose melphalan, be it single or double, was surprisingly negative. It did not show the difference that was expected from the original design. 

Now, does that mean that one shouldn’t offer transplant to patients? Obviously not. It doesn’t mean that. What it means is that the benefit of MRD in particular settings or improving MRD in particular settings may be limited. And I think as we think about tandem transplant, the fact that that didn’t add substantially to MRD improvement in that particular arm of the study is noteworthy. And I think similarly for the standard risk MRD negative patients, the use of single transplant didn’t appear to meaningfully improve MRD rate for those patients. So putting that all together, I think as we think about the clinical trial and its implications, I think it’s very thought provoking. It suggests to us that we can be more tailored in our approach to patients, that MRD negative standard risk patients can potentially keep transplant in reserve. And at the same time, we can be in a situation where patients can have choices as they approach whether or not to use high-dose therapy. And the field as a whole, of course, is now looking at immune treatments. And these new immune therapies are likely to substantially change our treatment paradigm. And so with all of that in mind, I think it’s a great time to think creatively about best treatment options for our patients in the newly diagnosed, transplant eligible setting.

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