Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings

Abstract

Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75years) or those ineligible for induction chemotherapy due to co-morbidities. In this phase 1/2 study (NCT02265731), Japanese patients (≥60years) with untreated (ineligible for induction chemotherapy) or relapsed/refractory acute myeloid leukaemia received oral venetoclax 400mg/day (3-day ramp up in cycle 1) plus subcutaneous or intravenous azacitidine 75mg/m2 on days 1-7 per 28-day cycle until disease progression or unacceptable toxicity. As of 10 December 2019, six patients were enrolled (median age: 75years; untreated: n=5; relapsed/refractory: n=1); median treatment duration: 10.3months (range, 0.7-29.4). Most common grade≥3 adverse events were lymphopaenia and febrile neutropaenia (n=4 each). Four patients reported serious adverse events; only an event of grade 3 fungal pneumonia was considered possibly related to both study drugs, requiring dose interruption of venetoclax and delay of azacitidine. Five (83%) patients had responses (complete remission: n=3). Median time to first response of complete remission/complete remission with incomplete count recovery was 1.0month (range, 0.8-5.5); median overall survival: 15.7months (95% confidence interval: 6.2, not reached). Venetoclax plus azacitidine was well tolerated and showed high response rates in Japanese patients with acute myeloid leukaemia.