ASH 2023 | Current and emerging treatments for MF: an update from ASH 2023

This has been a particularly happening ASH meeting for myelofibrosis research. There’s been, I’ve never seen, you know, as much excitement, as much interest and engagement as we have seen this year.There have been a number of important studies reading out, most importantly, a couple of Phase III studies of navitoclax and pelabresib. We saw some really interesting, encouraging, intriguing results, particularly with pelabresib, which was the larger of the two studies. So one approach moving forward is, of course, these types of synergistic combinations. Of course, it remains to be seen whether one or both of them is approved, but we saw a lot of positives, for example, from the pelabresib trial.

Now these two would be the furthest along, in terms of them being in Phase III, but there are quite a few other novel mechanisms of action beyond JAK inhibition that have also been reported out at this meeting, some by themselves. For example, the Sumitomo PIM kinase inhibitor TP-3654, and others in combinations, for example, selinexor, the XPO1 inhibitor from Karyopharm in combination with ruxolitinib.

So there’s been a lot of really interesting drugs presented, two other BET inhibitors beyond pelabresib, one from BMS, one from insight, we just talked about zilurgisertib, that’s an example of an anemia drug. So really the field is moving towards JAK inhibitors as a backbone, but then adding on other treatments either to synergize and give us a deeper remission, more long lasting remission, disease modification, as it is often called, it is becoming a cliche these days, but really something that impacts long term outcomes over and above what JAK inhibitors alone can do, or adding a drug to JAK inhibitors to counteract that anemia so as to be able to deliver a more effective dose of a JAK inhibitor for a longer period of time. So I think these are two ways in which the field is absolutely moving forward.

There are other ways as well. There are, you know, for example, our group actually presented, a cellular therapy abstract at this ASH meeting, which are umbilical cord derived regulatory T-cells, which you add to a stable dose of ruxolitinib. Now that would be the first foray into immunotherapy in myelofibrosis, that’s just another example. Then there are ways of targeting mutant calreticulin that are coming down the pike. So there is a lot happening, way more than I can summarize in these few minutes, but that gives you a flavor of things to come.