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EBMT 2021 | Monoclonal antibodies for myeloma relapsed after ASCT

Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, outlines the use of monoclonal antibody therapies for patients with multiple myeloma who relapse after autologous stem cell transplantation (ASCT). Prof. Mohty compares treatment options for patients who are lenalidomide-refractory and patients who are lenalidomide-sensitive. For lenalidomide-sensitive patients, Prof. Mohty highlights data from the Phase III POLLUX trial (NCT02076009) investigating daratumumab-lenalidomide-dexamethasone in patients with R/R multiple myeloma. For patients who are lenalidomide-refractory, Prof. Mohty discusses results from the CANDOR trial (NCT03158688), testing daratumumab-carfilzomib-dexamethasone, and the IKEMA trial (NCT03275285), investigating isatuximab-carfilzomib-dexamethasone, both in patients with R/R multiple myeloma. Finally, Prof. Mohty discusses the use of IMiDs, with reference to the APOLLO trial (NCT03180736) investigating daratumumab-pomalidomide-dexamethasone, and the ICARIA-MM trial (NCT02990338), investigating isatuximab-pomalidomide-dexamethasone. This interview took place during the 47th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2021.

Transcript (edited for clarity)

Stem cell transplantation is really standard of care for patients who are young and fit. And definitely, this is really the treatment which is providing the longest progression-free survival. And this has been shown in different randomized Phase III trials from different groups, including long-term follow-up.

However, unfortunately we need to acknowledge that auto-transplant is not a curative procedure and these patients are going to relapse after a transplant...

Stem cell transplantation is really standard of care for patients who are young and fit. And definitely, this is really the treatment which is providing the longest progression-free survival. And this has been shown in different randomized Phase III trials from different groups, including long-term follow-up.

However, unfortunately we need to acknowledge that auto-transplant is not a curative procedure and these patients are going to relapse after a transplant. This is why the choice of the treatment of first relapse, so second-line treatment or treatment of first relapse, is really crucial because now we do have some very powerful combinations. And here, I think we have to distinguish those patients who relapsed after transplant and have received continuous lenalidomide. And this is the group of patients who would be considered as lenalidomide-refractory. And then you have the other group of patients who may not have received the lenalidomide maintenance, or they may have received lenalidomide for a limited duration. So, they remain lenalidomide-sensitive and can be re-challenged with lenalidomide.

So, in this group of patients who are still sensitive to lenalidomide, obviously daratumumab-lenalidomide-dexamethasone, as it has been shown in the POLLUX trial is really a very powerful treatment option. We do have now a long-term follow-up for the POLLUX trial and the results when it comes to first relapse after auto, for instance, are quite impressive. So this recommendation is definitely very important.

When it comes to the patient who are lenalidomide-refractory, obviously you need to have to switch gears. And again, it has to do because we’re focusing on antibody-based salvage treatments. It has to do with the best partner to the anti-CD38 antibody. And here we have the results of the CANDOR trial. Very important data in this population, showing that daratumumab-carfilzomib-dexamethasone is a great option.

We do have the IKEMA trial with isatuximab-carfilzomib-dexamethasone. If for some reason one would like to give an IMiD, then obviously you need to use the pomalidomide based combinations, namely Dara-POM-Dex or isatuximab-POM-Dex.

Obviously the different populations that were included in these trials, whether CANDOR, whether IKEMA, whether APOLLO, Dara-POM-Dex, or ICARIA, the isatuximab-POM-Dex, are different and it’s very difficult to compare. But here I wanted just to highlight the global picture about how to use these combination for first relapse after transplant. And the key message in my opinion is that we should not miss this step of first relapse because you can achieve, in these patients, a relatively long progression-free survival, which can be as long or even longer than what we can achieve in patient in first line. So, the treatment of this group of patient is quite promising and brings lots of hope.

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