Efficacy of the Combination of Venetoclax and Azacitidine in Elderly of Frail Relapsed/ Refractory Patients with Acute Myeloid Leukemia, First Multi-Institutional Real World Experience from Turkey

Abstract

Acute myeloid leukemia (AML) usually seen in the elderly. The quest for effective, tolerable and durable response for the treatment of elderly or frail patients with AML resulted venetoclax combination. The aim of this study was to present here the experience and data for the use of venetoclax in combination with azacitidine in elderly or frail and unfit patients with relapse/refractory AML treated outside of a clinical trial. We retrospectively analyzed 30 consecutive elderly (≥ 65 years old) or frail patients with relapse/refractory AML, who failed at least one prior therapy for AML and treated with venetoclax in combination with 5-azacitidine at five institutions in Turkey between December 2018 - Januarry 2020. The patients were taken venetoclax at dose of 400 mg daily, and 75 mg/m2/day azacitidine subcutaneously for 7 days per 28-day cycle. Complete remission (CR), incomplete blood count recovery (CRi), PR, overall survival (OS) and event free survival (EFS) were assessed. A total of 30 patients with a median age of 67 (range= 33-84) from 5 differ- ent centers were included in the final analysis. Overall response rate (ORR) was 63.3% (n= 19); 15 (50%) patients achieved CR or CRi and 4 (13.3%) patients achieved PR while 11 patients (37.7%) did not respond to therapy. Median 8 months follow-up, 6 months OS rate 66.7%, 1-year OS rate was 19.8% with a median OS was 7 months (95% CI: 7.8 -10.1). The mortality risk of patients under 60 is statistically significantly lower than those over 60 (p= 0.007, HR: 0.109 (95% CI: 0.022 - 0.55). Combination of venetoclax + HMA in patients with relapse refractory AML with poor performance score, it provided somewhat higher response rates and additionally, the responding patients benefited surival advantage when compared to non-responding patients. Keywords: AML, Elderly, Venetoclax, Azacitidine, Survival