ASH 2025 | The evolving role of autoSCT in NDMM: an overview of clinical trial evidence

The topic of autologous stem cell transplant in multiple myeloma newly diagnosed patients who are transplant eligible, this topic is still an open situation and during the last ASH meeting this has been addressed once more and despite there being more and more data in favor of very successful induction regimens questioning the role of high-dose melphalan, but at the end of the day, our position is the same. And this year, when the EMN-EHA guidelines for multiple myeloma treatment were published, stem-cell transplant kept its position. And at the end of ASH, the Mayer group MSMART algorithm was updated, again, keeping the same as stem cell transplant in standard risk as a deferral position, but for high risk, certainly standard of care. And what is the difference now with the new data coming in? In the old traditional questioning the role of stem cell transplant approach, what was done was comparing autologous stem cell transplant after an induction, comparing with a consolidation treatment. And this type of approach, the old EMN-02 study, for instance, was in favor of stem cell transplant. And later, this was criticized by the weakness of the induction being just VCD.

And during the last couple of years, quadruplet regimens, such as DARA-VRD or ISA combinations, VRD or KRD, have been introduced with very successful outcomes after induction. So the role of stem cell transplant is no longer a comparison between transplant versus consolidation. But looking at the post-induction response that is measured by a measurable residual disease negativity and then randomizing patients towards either transplant yes or no. And this type of approach is now kept in the MIDAS study and also MASTER-2 study. And both are addressing the role of MRD-based certification. And the results of these two studies are expected to be published next year. And before that, it is hard to change the role of stem cell transplant.

And on the other hand, what can be done is looking at the depth of response prior to stem cell transplant and after melphalan. And this is possible now with newer regimens. And the newer induction regimens are not only the quadruplets, but adding the bispecifics on top of either the triplet or even the quadruplet. So now, for instance, in the MajesTEC-5 and German HDD10 study, and the combination of either DaraRD with TEC or TAL or with VRD, this type of regimen induces almost 100% of MRD negativity after induction. And so the impact of high-dose melphalan in this setting is really questionable. And if there’s no added value of stem cell transplant in this type of very intensive regimens, then this may change our approach in future.

And so to approach this in a different way, there is another study, which is the IMMUNOPLANT study, which was presented at the ASH meeting. The design of the study is such that after an induction regimen, when the patients reach MRD negativity, instead of continuing with the induction regimen, linvoseltamab and other BCMA bispecific was introduced to continue with therapy. So instead of using autologous stem cell transplant and high-dose melphalan as the intensification treatment, instead using a bispecific as a consolidation. And in this Phase II study, early results show a very frequent rate of MRD negativity, which is again a promising finding. So for at the time being, stem cell transplants, high-dose melphalan is standard of care for high-risk patients even now. And for standard risk patients, if we are just giving quadruplet regimens, in that case reaching MRD negativity after induction four to six cycles later, then in that case, deferral of stem cell transplant is generally accepted. But otherwise, the role of stem cell transplant and to replace that with the new immunotherapies is not prime time yet. And when it comes to relapse, on the first relapse, we have very effective regimens such as CAR-T. And so frontline use of CAR-T will add another perspective into this field. So there’s much to see in the near future.

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