Glasdegib in combination with azacitidine in patients with untreated higher-risk myelodysplastic syndromes and AML

Dr Mikkael Sekeres - Cleveland Clinic, Cleveland, USA

There are actually a few studies that we’re presenting at the annual meeting that I’m really excited about. The first is a phase 1b study of the hedgehog inhibitor glasdegib that has been combined with azacitidine in patients with AML and MDS. The reason the study is important is because glasdegib is actually FDA approved in combination not with a hypermethylating agent but with low dose cytarabine. It was FDA approved based on a survival advantage for the combination versus low dose cytarabine alone. The reason our study is important is because for the first time glasdegib has been combined with azacitidine which is used far more commonly in the US and in other parts of the world.

In this study we enrolled a total of 60 patients, 30 with AML and 30 with higher risk MDS. We found that the remission rates or hematologic improvement rates for those with MDS was about one third and the CR, CRi and PR rates for those with

AML was about 30%. The median overall survival for these groups for those with AML was slightly over nine months and for those with MDS was over 15 months.

The conclusion of that study is that the response rates and overall survival were quite comparable, if not better, to the combination of glasdegib with low dose cytarabine. So it appears that it can be used safely and effectively in combination with azacitidine.