EHA 2025 | An update on immune checkpoint inhibition in MDS & AML: investigating sabatolimab and bexmarilimab

Today I spoke about an update on the immune checkpoint inhibition use in MDS and AML. The audience will know that immune checkpoint inhibition in AML and MDS has been something that has been a little bit frustrating because we saw very nice results in solid tumors, but using the traditional approaches of anti-PD-1, PD-L1, CTLA-4 has not yet shown very promising results in AML and MDS. So today I overviewed some of the results and why this has been kind of the situation, but I also looked towards the future and some of the more exciting data that is being generated now. 

So we talked about sabatolimab, which is an anti-TIM3 antibody that had technically a negative Phase III trial with a median survival prolongation with AZA, sabatolimab versus AZA in a large international study, more than 500 patients with a 3.8 month survival, but this was not statistically significant. But what we showed in this meeting that when you actually analyze the data by sex, women actually had a very impressive overall survival difference of 26 months compared to 18 months, an 8-month difference, while men did not have that. So most of the survival benefit was driven by women. And we talked about why this could be the case, because there could be some differences in the immune landscape and in the bone marrow microenvironment in women, and they might be more amenable to immune modulation. 

But also we talked about some of the novel antibodies that are being tested, for example, bexmarilimab, which is an anti-CLEVER-1 antibody. And I think this is a very interesting pathway. CLEVER-1 is expressed on macrophages. It suppresses the macrophages, and it has been shown to be overexpressed in some cancers, including AML and MDS, and targeting it with antibodies such as bexmarilimab has been shown to activate these macrophages and lead to basically tumor responses. So in this meeting, actually, Dr Kontro, my colleague, is presenting data on behalf of the investigators looking at bexmarilimab in the Phase II part of the study in combination with azacitidine, where we are seeing very good responses both in the second line after HMA failure and the front line setting. So the drug is well tolerated and the data is very promising. And I think one of the things we are discussing right now with the regulators is how to move this drug development further, hopefully towards a Phase III trial, and hopefully this will kind of break the cycle of negative data in immune checkpoint inhibition in AML and MDS.

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