Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings.
BACKGROUND
Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75 years) or those ineligible for induction chemotherapy due to co-morbidities.


METHODS
In this phase 1/2 study (NCT02265731), Japanese patients (≥60 years) with untreated (ineligible for induction chemotherapy) or relapsed/refractory acute myeloid leukaemia received oral venetoclax 400 mg/day (3-day ramp up in cycle 1) plus subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7 per 28-day cycle until disease progression or unacceptable toxicity.


RESULTS
As of 10 December 2019, six patients were enrolled (median age: 75 years; untreated: n = 5; relapsed/refractory: n = 1); median treatment duration: 10.3 months (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 1.0 month (range, 0.8-5.5); median overall survival: 15.7 months (95% confidence interval: 6.2, not reached).


CONCLUSIONS
Venetoclax plus azacitidine was well tolerated and showed high response rates in Japanese patients with acute myeloid leukaemia.
['Taniguchi|Shuichi|S|', 'Yamauchi|Takahiro|T|', 'Choi|Ilseung|I|', 'Fukuhara|Noriko|N|', 'Potluri|Jalaja|J|', 'Salem|Ahmed Hamed|AH|', 'Hong|Wan-Jen|WJ|', 'Honda|Hideyuki|H|', 'Nishimura|Yasuko|Y|', 'Okubo|Sumiko|S|', 'Usuki|Kensuke|K|']
D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D001374:Azacitidine D019086:Bridged Bicyclo Compounds, Heterocyclic D005260:Female D006801:Humans D007564:Japan D015470:Leukemia, Myeloid, Acute D008297:Male D012074:Remission Induction D013449:Sulfonamides D016019:Survival Analysis D016896:Treatment Outcome
AML BCL-2 Japan anti-neoplastic agents apoptosis