EHA 2025 | Final results of a pilot study of elotuzumab in patients with myelofibrosis

So, elotuzumab is a SLAMF7 monoclonal antibody. So, a number of years ago, our group, led by Serge Verstovsek, had shown pre-clinically that the fibrosis in myelofibrosis is really driven by these fibrocytes, which are sort of these fibrosis engendering cells in the bone marrow, and these fibrocytes in turn are developed from monocytes. So they are monocyte derived, monocytes differentiate into fibrocytes and that then leads to the fibrosis. Now it has been long held that fibrosis is a reactive phenomenon in myelofibrosis driven by cytokines, inflammatory milieu, etc. However our group was able to show and this is going back to 2016 that these cells that drive the fibrosis are in fact clonal, neoplastic, they contain, they express the driver mutation. So this was really, you know, a pretty novel finding that challenged the notion at the time. The long held notion that this is, you know, a reactive process. So this seemed, you know, this was a pretty remarkable finding. And then what this led to actually, know not to digress but just briefly pertinent to mention that this led to investigations of a drug called PRM151 or zinpentraxin alfa which has since been discontinued but that was one of the first you know major efforts to develop an anti-fibrotic agent and that agent you know is not being not being pursued anymore but that work came directly out of out of the preclinical work that I mentioned. Now more recently Japanese colleagues in I think 2017 and 2019 published that SLAMF7 is a target in these monocytes that then differentiate into fibrocytes and drive the fibrotic process and that gave us the idea to study elotuzumab which is a commercially available monoclonal antibody against SLAMF7 for multiple myeloma. And so, we partnered with BMS for this study who kindly supported the drug and as well as provided some support for this investigator sponsored study. 15 patients all accrued at this point. In fact, only one remains on the study. I’ll just mention a few, I think, points to note. One, there were quite a few patients who stayed on study for the full three years. So 36 months was sort of the max as stipulated in the protocol and quite a few patients, I want to say maybe four or so out of the 15, made it that entire time and came off because the study was over at that point. And what we saw were, we saw several IWG MRT responses. We saw anemia responses, platelet responses, symptom responses. We saw all of that, not spleen. And in terms of fibrosis, now ironically we didn’t see much of an improvement there at least by our conventional grading system for bone marrow fibrosis. We did see one patient that went from MF3 all the way to MF1 but I don’t think we saw you know notable fibrosis responses in the others. However again like I said there were platelet responses, symptom responses and anemia responses.

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