Hypomethylating agents+venetoclax induction therapy in acute myeloid leukemia unfit for intensive chemotherapy - novel avenues for lesser venetoclax duration and patients with baseline infections from a developing country.

Abstract

Both elderly acute myeloid leukemia (AML) patients and those with baseline infections, when treated with intensive chemotherapy, are associated with high induction mortality. We report 24 patients (16-newly-diagnosed, 8-relapsed/refractory) with AML deemed unfit for intensive chemotherapy (by virtue of age >60 years, ECOG-PS 3-4, or those with non-resolving infections at baseline), treated with azacytidine-venetoclax combination as induction chemotherapy. Median follow-up of the study group was 8 months. The overall complete remission (CR)+CR with incomplete count recovery (CRi) rate was 58.3%. 1-year progression-free survival and overall survival of the whole cohort was 44.4% and 55.8%, respectively. On subgroup analysis, newly-diagnosed AML (p=0.05), intermediate-risk cytogenetics (p=0.007), and HMA-naïve (p=0.05) patients had a significantly better outcome. AML patients with baseline infections (versus without infections) treated with azacytidine-venetoclax induction, have lesser induction mortality (compared with historic intensive chemotherapy) with equivalent response rates. A detailed analysis amongst cohorts with different venetoclax durations revealed that, shorter duration (<21 days) venetoclax (versus 21-28 days duration) in induction therapy leads to similar response rates and similar severity of myelosuppression, however, with early count recovery and lesser duration of intravenous antibiotics.