Jacqueline Garcia, MD, of Dana-Farber Cancer Institute presented at #ASH24 data suggesting oral maintenance therapy with venetoclax and decitabine/cedazuridine after HCT is safe, feasible, and may reduce relapse rates in high-risk AML/MDS patients.
Most of our patients with these diseases are older and are thus recommended for reduced intensity conditioning. That's called a RI transplantation. Rick transplantations, however, are not successful in patients that have persistent measurable residual disease. We'll call that MRD. And so if patients have pre-transplant measurable residual disease, it increases the chance of relapse risk. And for our patients that are undergoing a RIC transplant, which is the majority of our patients above the age of 60. This means that they're at high risk for relapse. So one of the strategies that we're trying to employ here is to provide continuous low doses of an AML-directed regimen without interfering with transplantation. Here at Ash, I showed the data from a 30 patient cohort where we attempted to give maintenance. after patients got a modified genetic clacks plus Airbnbs and reduced intensity conditioning strategy. Patients engrafted 3 patients came up study due to relapse, but otherwise 26 patients, or 87%, were able to receive planned maintenance therapy or initiate it. We offered maintenance therapy with an all oral regimen on a 42 day cycle with Venetoclaxs given at 14 days at 400 mg, and oral decitabine such as uridine, we'll call this oral decitabine. Given days 135 or days 1 through 3, so at these two different dose levels, what was really exciting to see is that the median doses delivered or cycles delivered were 8, which was the plan intended number of cycles, and so the majority of patients, unless they relapsed or had an issue on trial, were able to receive therapy, which is encouraging, showing tolerability. Uh, in terms of the toxicities for those that received maintenance therapy, there were no grade 3 or 4 non-hematologic toxicities, but there were expected heme toxicities including lower blood counts that are expected. We did observe neutropenia and thrombocytopenia, which is the lowering of neutrophils and platelets that were expected brief and self-resolving and on time at the end of each cycle. We did note that there was one grade 3 febrile neutropenia event and one grade 3 sepsis event, but otherwise this regimen was well tolerated. Growth factor support was not needed during maintenance therapy, but antibacterial support was provided which prevented infectious complication. T cell chimerism occurred on schedule and on time compared to what we've seen historically, and the graft versus host disease rate at 1 year for those with moderate or severe chronic GVHD was low at 16%. From our regimen, what we could see after 22 months of follow up, which is a reasonable amount of time for an early trial like this, we see a 1 year overall survival at 81%. One year progression free survival at 73% and 1 year cumulative incidence of relapse at 27%, which I think is really encouraging for a high risk population undergoing transplantation. So in summary at this year's AS we were able to demonstrate the safety, feasibility, and early efficacy of an all oral maintenance strategy for patients with high risk mild dysplasia syndrome and high risk acute myelo leukemia that undergo a reduced intensity transplantation.
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