Investigational Studies and Therapies in MDS

David Sallman, MD, myeloid section head and associate member of the Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, discusses some of the innovative therapies and strategies being investigated in myelodysplastic syndromes (MDS) studies.

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0:09 | The 1 trial we are maybe most eagerly awaiting for is the VERONA trial [NCT04401748], which is a phase 3 trial of azacitidine with venetoclax versus azacitidine therapy alone. Of course, in AML, this has very much changed the standard-of-care for elderly AML, although it is impacting many patients in all different situations. So, it is a relatively similar type design. I think in MDS, we know that the cytopenia toxicities are a little bit less well tolerated, and thus, we have a lower schedule of venetoclax. There has been a large phase 1, borderline phase 2 study presented by Jacqueline Garcia, MD, at ASH where there are 107 patients, and response rates, at least from composite [complete] response [CR] rates, are significantly higher. Data from our center that we published look relatively identical from that perspective. But…we need to improve overall survival. That is really the key primary end point of the trial, and so that is what we are currently waiting on. I think particularly for patients that can go to allogeneic stem cell transplant, the therapy is very effective. I think it really does induce deeper and what I would call [minimal residual disease (MRD)]-negative remissions, which not has not really been a thing in myelodysplastic syndrome. But I think that the balance of what percentage of patients get there may tip whether or not the trial is positive or not. Although, I think the utilization, at least in the United States, will still be significantly high. They kind of went over those data in detail. Again, we need that trial.

1:33 | The 1 other main study that we hope to have data by the end of the year is the SELECT-MDS-1 [NCT04797780], which is a phase 3 trial of azacitidine/tamibarotene vs azacitidine alone. This is a little bit for a biomarker-specific group. You have to have what is called RARA overexpression, which is about 50% of MDS patients. What we are going to know at least by the end of the year is the CR rate in the first 190 patients. The trial is actively occurring up to over 500 patients with a secondary end point of overall survival. Hopefully, we are going to have both of these data, maybe by the end of the year, and maybe finally, changing that frontline landscape because the whole field is a little bit in a lull, I would say, with a lot of negative trials, and then whether or not the standard-of-care is changing or is not changing, or do we need to start from scratch and completely redesign these type of studies.