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The 2022 Tandem Meetings | Sorafenib or venetoclax in fractionated busulfan conditioning regimen for AML & MDS

Uday Popat, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, shares the findings of a study evaluating the addition of sorafenib and venetoclax to a fractionated busulfan conditioning regimen in patients with higher risk acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), highlighting the benefits of such conditioning regimens. Extending the conditioning regimen over a longer period of time allows to reduce toxicity without impacting efficacy, and allows to add oral targeted agents such as sorafenib and venetoclax. Overall, the study defined the optimal dose of sorafenib and reported a one-year progression-free survival (PFS) of 90%. Despite a relatively short follow-up, the study showed that venetoclax was very well tolerated in these patients. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.

Transcript (edited for clarity)

So this is, again, the third generation addition to this trial. So one of the beauties of fractionating the busulfan or extending the regimen over three weeks is, we not only reduce the toxicity, without reducing the impact on efficacy, we also have a longer period where we can give the targeted agent. So if you think about it, a drug like sorafenib needs to be given orally for multiple days. And if you have a regimen that just spans over a week or four days, you really don’t have that drug to have an effect...

So this is, again, the third generation addition to this trial. So one of the beauties of fractionating the busulfan or extending the regimen over three weeks is, we not only reduce the toxicity, without reducing the impact on efficacy, we also have a longer period where we can give the targeted agent. So if you think about it, a drug like sorafenib needs to be given orally for multiple days. And if you have a regimen that just spans over a week or four days, you really don’t have that drug to have an effect. But this gave us the perfect platform to add oral targeted agents. So we are presenting two separate abstracts in an oral presentation, one on sorafenib and one on venetoclax. So in the first trial, what we show is that the optimal dose of sorafenib is 400 milligrams twice a day when added to a myeloablative fractionated busulfan regimen. And with that, we are seeing one-year progression-free survival of close to 90 in about 90% in about 24 patients. Obviously, With this dose, we are now taking it to a Phase II setting, and a larger trial is underway. We use the same principle and added venetoclax, which has been shown very useful when added to things like azacitidine, or even conventional chemotherapy, in improving remission rate and reducing relapse rate in patients with AML. So we added venetoclax, 400 milligrams, to a standard three weeks or two weeks fractionated busulfan regimen. And what we find again, is it is very well tolerated. So the initial data, in more than 30 patients, we show that this is safe. And again, the day early data are encouraging. The follow-up is short. But I think we have already started a next generation of trials using this particular agent at 400 milligrams per day, with this regimen in higher risk AML and MDS groups, to see if we will see any reduction in relapse rate.

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