EBMT 2022 | Optimizing the outcomes of autoHSCT in multiple myeloma
Autologous hematopoietic stem cell transplantation (autoHSCT) is the current standard of care (SOC) for newly diagnosed multiple myeloma (NDMM). In this video, Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, comments on strategies to improve patient outcomes after autoHSCT by optimizing induction and maintenance therapies. The combination of proteasome inhibitors, immunomodulatory imide drugs (IMiDs) and corticosteroids has been used as induction therapy for patients with NDMM. However, recent data from clinical trials has demonstrated the superiority of quadruplet induction therapy with daratumumab. Similarly, several studies have reported positive results for the combination of lenalidomide with proteasome inhibitors or daratumumab, thus challenging the use of single-agent lenalidomide, which is the current SOC maintenance strategy for NDMM. Together, combining optimal induction and maintenance strategies will allow patients to achieve deep and sustained measurable residual disease (MRD) negativity. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.
Transcript (edited for clarity)
Autologous stem cell transplantation for newly diagnosed multiple myeloma is likely here to stay because when we look to the key and biggest randomized Phase III trial, they are all in favor of transplant frontline, not delaying transplant. So the question is “how can we further improve the results of autotransplant in multiple myeloma?” And I think we’ve seen over the last couple of years, the advent of some interesting results, but also combinations when it comes for instance, to improving the induction regimens...
Autologous stem cell transplantation for newly diagnosed multiple myeloma is likely here to stay because when we look to the key and biggest randomized Phase III trial, they are all in favor of transplant frontline, not delaying transplant. So the question is “how can we further improve the results of autotransplant in multiple myeloma?” And I think we’ve seen over the last couple of years, the advent of some interesting results, but also combinations when it comes for instance, to improving the induction regimens. Until recently we’ve been relying on triplet combinations, proteasome inhibitors, IMiDs, Dexamethasone, like the famous VRD or VTD regimens. But now I think, and there is also already an approval that the future, the near future is about using quadruplet combinations. And this is why adding anti-CD38 monoclonal antibodies like daratumumab to VTD or VRD is proving to be very promising. Dara-VTD showed superiority in terms of response after induction in the CASSIOPEIA Phase III randomized trial. Dara-VRD showed superiority in the GRIFFIN Phase II randomized trial.
And in those trials now with sufficient follow up, we can see improvement, a trend towards an improvement in progression-free survival. So using a quadruplet based induction is likely to be positively impactful later for the outcome of the patient. But I believe things will also improve because there is now a clear recommendation to continue consolidation after transplant, but also to use maintenance. And until recently lenalidomide was the only approved and widely used option. However, again, this field is moving very rapidly and we’ve seen studies showing the proof of concept about the feasibility of doublet maintenance. And again, we have data combining second-generation proteasome inhibitors and lenalidomide, like in the FORTE trial, carfilzomib and lenalidomide. And we’ve seen also in the GRIFFIN trial, the use of daratumumab and lenalidomide. Obviously these doublets are not yet approved for maintenance, but I think the feasibility is there, and the results look promising.
So we are eagerly awaiting for the results of randomized Phase III trials, because obviously this will help further improving the results because at the end of the day, actually, when you combine the optimal induction, namely a quadruplet, when you use high-dose chemotherapy melphalan 200, you use consolidation, but also if you are able to optimize your maintenance strategy, this is where you are likely going to be able to put the patient, to bring patient into the deepest, minimal residual disease. And we know very well that if you are able to achieve a deep, but also sustained MRD negativity, these are the patients who are really going to do well over the long term.
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