Response patterns and impact of MRD in patients with IDH1/2-mutated AML treated with venetoclax and hypomethylating agents
Danielle Hammond, Sanam Loghavi, Sa A. Wang, Marina Konopleva, Tapan M. Kadia, Naval Daver, Maro Ohanian, Ghayas C. Issa, Yesid Alvarado, Nicholas J. Short, Koji Sasaki, Naveen Pemmaraju, Guillermo Montalban‐Bravo, Curtis A. Lachowiez, Abhishek Maiti, Guillermo Garcia‐Manero, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, Koichi Takahashi, Sherry R. Pierce, Hagop M. Kantarjian, Courtney D. DiNardo
Abstract
Several lower-intensity therapies for isocitrate dehydrogenase 1/2 ( IDH1/2 )-mutated AML are available (Supplemental Table 1 ), including small molecule inhibitors of mutant IDH1 (ivosidenib and olutasidenib) and IDH2 (enasidenib), used alone or in combination with broader anti-leukemic agents. While not molecularly targeted therapy per se, venetoclax-based therapy has preferential activity in IDH1/2 -mutated disease [ 1 , 2 , 3 ]. Given uncertainty surrounding the optimal sequence of these agents, we investigated the quality and duration of responses to venetoclax and hypomethylating agent (VEN + HMA) combinations in IDH1/2 -mutated AML. We additionally characterize response patterns in a subset of these patients who were consecutively treated (either directly before or after VEN + HMA) with IDH inhibitor (IDHi)-based regimens.