My name is Dr. Paul Richardson and I am the clinical program leader and director of clinical research at the Jerome Lippert Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston, Massachusetts. So another very important event this summer has been the reporting by our French colleagues under the leadership of Dr. Auroré Perrault of the results of the MIDAS trial. This I think has been one of the most important upfront transplant studies to date and this is a study where she has used MRD adapted approaches and risk adapted approaches to the use of high dose therapy in transplant eligible patients. The study has been platformed on the use of KRD plus isotoxamab, so a quadruplet combining carfilzomib with lenalidomide, dexamethasone and isotoxamab as an induction or omission strategy and then in standard risk MRD negative patients assigning them to either a single transplant followed then by maintenance or continued KRD isotherapy and then assessing MRD after those approaches versus in the high risk patients and the patients who are MRD positive, these patients have been assigned to either a single transplant or a second transplant in order to assess really the benefit of high dose melphalan in this population overall. Now, Auroré's results have been really quite eye catching and been very important. What she's shown is that the MRD rates generated by the quadruplet therapy have been remarkably high, regardless of the patient population, but in that same context, the use of single transplant in the MRD negative standard risk patients has to everyone's surprise I think, not meaningfully improve the MRD rate, suggesting that MRD guided treatment can inform us about certain patients who may be able to keep transplant in reserve, at least in the standard risk population. Now for the high risk population, as defined by the study, in that context, the use of single transplant was compared to two transplants. And again, what was seen here was that the second transplant surprisingly did not add much in terms of benefit to an improvement in MRD rate. And so this raised the question of how much value is there to that second transplant. And so one conclusion from the study was that the use of two transplants in the majority of patients who may be high risk and or MRD positive did not seemingly convey benefit. So putting it all together, the relative value of adding high dose melphalan to every patient of the transplant eligible population can now be sort of called into question and we can say to ourselves, is transplant necessary in all patients? Or can we reasonably keep it in reserve, say for example, in standard risk MRD negative patients? Certainly in that setting, these data validate that approach. Now it's important to note that this was first suggested by the determination trial, where we were able to show that in standard risk patients, whilst there was BFS benefit to transplant, there was no overall survival benefit on the one hand. But most importantly, for our MRD negative patients, regardless of how they achieved it, either with RVD followed by transplant or RVD alone, their outcomes appeared to be very similar. So this MITRE study was very important because it went that much further to test this question and in fact showed something equally, I think, vital for patients. That in the correct setting, collecting stem cells, keeping transplant in reserve is a reasonable option. Conversely, however, transplant may definitively have a role for those patients with higher risk features and indeed requiring additional therapy. There clearly, transplant may be important. And then the final piece of this is with all the exciting immune treatments that we have, we're now in a position to meaningfully test how valuable they are compared to the standard of high dose melphalan and do so in a way where we can really hope to further improve patient outcome.
HealthTree • June 23, 2025