Impact of Venetoclax and Azacitidine in Treatment-Naive Patients with Acute Myeloid Leukemia and IDH1/2 mutations.

Evaluate efficacy and safety of venetoclax+azacitidine among treatment-naïve patients with IDH1/2 mutant (mut) AML.Data were pooled from patients enrolled in a Phase 3 study (NCT02993523) that compared patients treated with venetoclax+azacitidine or placebo+azacitidine and a prior Phase 1b study (NCT02203773) where patients were treated with venetoclax+azacitidine. Enrolled patients were ineligible for intensive therapy due to age {greater than or equal to}75 years and/or co-morbidities. Patients on venetoclax+azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle).IDH1/2mut were detected in 81 (26%) and 28 (22%) patients in the venetoclax+azacitidine and azacitidine groups. Composite complete remission (CRc, complete remission [CR]+CR with incomplete hematologic recovery [CRi]) rates (venetoclax+azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In the IDH1mut, CRc rates were 66.7%/9.1% and mOS 15.2/2.2 months. In IDH2mut, CRc were 86.0%/11.1%; mOS not reached (NR)/13.0 months. In IDH1/2 WT AML treated with venetoclax+azacitidine with poor-risk cytogenetics had inferior outcomes compared to IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax+azacitidine group.Patients with IDH1/2mut who receive venetoclax+azacitidine had high response rates, durable remissions and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.