VIDEO: Recent advancements in myelodysplastic syndrome

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The recent advancements that have been made have really been focused, predominantly, in the lower-risk myelodysplastic syndrome, and predominantly for patients that have RBC transfusion dependence. So, there have been actually two major advancements, I would say, in the past year. One is with a drug called luspatercept, or Reblozyl (Celgene, Bristol Myers Squibb), where this has already been approved for a subtype of patients that are MDS with ring sideroblast after prior therapy with the erythropoietin stimulating agents. But, there was a major frontline trial, called the COMMANDS trial. This was presented at ASCO/EHA of 2023, and recently published in "The Lancet" journal. And this was a frontline head-to-head comparison of luspatercept versus erythropoietin stimulating agents, and showed that, luspatercept, overall, worked better, as far as a much higher rate of transfusion independence. And this was in all-comer, lower-risk, myelodysplastic syndrome. So, we anticipate that there will be a label change, in the near future, supporting a frontline treatment option. And not only just for patients with MDS with ring sideroblast, but also for patients without ring sideroblast. I think there's a little bit of debate in the field. Clearly luspatercept seems to be the best drug right now for the MDS with ring sideroblast group. Whether or not it's really superior in the non-ring sideroblast group is still a question, there was a little bit of a smaller subset. Clearly there's a benefit, and I think this will be a nice additional tool for patients that have absence of ring sideroblast. I think where we use it pre- or post-erythropoietin stimulating agent is a little bit of a matter of debate, and I think things that will get figured out. The other big approval in the lower-risk myelodysplastic syndrome space that we're anticipating is with the drug imetelstat (Geron Corporatio). This was also presented at ASCO/EHA of 2023, and this is a first-in-class telomerase inhibitor. And this was essentially for ESA, or erythropoietin stimulating agent failure patients. Again, looking at transfusion independence and was, you know, significantly improved that versus placebo. I think what's a little bit exciting with the imetelstat is it didn't seem to matter. Ring sideroblast, not ring sideroblast, high transfusion burden, low transfusion burden. What was the baseline erythropoietin level? This is something that has been a challenge to prior therapies. And so, it seems like it may be a real good option for patients who really haven't responded well to past anemia-directed therapies. And then there's some hint of excitement. Could this even be a disease-modifying therapy? I think that question is definitely still out. But in some patients, where we have their mutations at baseline and we sequentially evaluated that, you know, subsequently some of these mutations were able to at least be significantly reduced. And I think we'll see some follow-up presentations, you know, on that, probably anticipating, let's say, for ASH of this year. So, that's probably the two, you know, agents. You know, again, one new label. One, again, we're anticipating an approval in the near future that are the most exciting, you know advancements that are going to impact patients. Now, as far as advancements in the higher-risk MDS setting, we've had a lot of setbacks, including a very recent major setback, called the ENHANCE trial. This was a phase three trial looking at azacitidine plus magrolimab versus azacitidine (Vidaza, Celgene) alone. And the only thing we have right now is a press release, that, you know, the trial did not meet its primary endpoint. And essentially magrolimab (Gilead), you know, is not being further investigated in MDS patients. You know, based on the trial, and again, we look forward to presenting and ultimately publishing these data. Because this is actually the largest, you know, phase three trial run in MDS, and one of the first ones to look for overall survival that has a readout. So, we're all looking for what combination with azacitidine can change our standard of care. There are still two phase three trials that have finished accrual that we're waiting for data. This is azacitidine with venetoclax (Venclexta; AbbVie, Genentech), as well as azacitidine with sabatolimab (Novartis). There's a little bit of concern with the sabatolimab program because a randomized phase two was presented at ASH and was ultimately negative. The only ongoing phase three trial is azacitidine plus tamibarotene (Syros Pharmaceuticals), as far as an accrual perspective, which is for patients that have what is called RARA overexpression. That trial is somewhat earlier on, but it is the current you know, ongoing study. And a little bit long-winded, but I think these are kind of, maybe, big picture. See the advancements that have been made and potentially the advancements that are coming hopefully in the not too distant future.