Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23861
Title: Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy.
Austin Authors: Chua, Chong Chyn ;Roberts, Andrew W;Reynolds, John;Fong, Chun Yew ;Ting, Stephen B;Salmon, Jessica M;MacRaild, Sarah;Ivey, Adam;Tiong, Ing Soo;Fleming, Shaun;Brown, Fiona C;Loo, Sun;Majewski, Ian J;Bohlander, Stefan K;Wei, Andrew H
Affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Australia
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia
Department of Haematology, Box Hill Hospital, Box Hill, Victoria, Australia
Department of Haematology, Austin Health, Heidelberg, Victoria, Australia
The Alfred and Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia
Department of Haematology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
Issue Date: Oct-2020
metadata.dc.date: 2020-07-20
Publication information: Journal of Clinical Oncology 2020; 38(30): 3506-3517
Abstract: The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax has an emerging role in acute myeloid leukemia (AML), with promising response rates in combination with hypomethylating agents or low-dose cytarabine in older patients. The tolerability and efficacy of venetoclax in combination with intensive chemotherapy in AML is unknown. Patients with AML who were ≥ 65 years (≥ 60 years if monosomal karyotype) and fit for intensive chemotherapy were allocated to venetoclax dose-escalation cohorts (range, 50-600 mg). Venetoclax was administered orally for 14 days each cycle. During induction, a 7-day prephase/dose ramp-up (days -6 to 0) was followed by an additional 7 days of venetoclax combined with infusional cytarabine 100 mg/m2 on days 1-5 and idarubicin 12 mg/m2 intravenously on days 2-3 (ie, 5 + 2). Consolidation (4 cycles) included 14 days of venetoclax (days -6 to 7) combined with cytarabine (days 1-2) and idarubicin (day 1). Maintenance venetoclax was permitted (7 cycles). The primary objective was to assess the optimal dose schedule of venetoclax with 5 + 2. Fifty-one patients with a median age of 72 years (range, 63-80 years) were included. The maximum tolerated dose was not reached with venetoclax 600 mg/day. The main grade ≥ 3 nonhematologic toxicities during induction were febrile neutropenia (55%) and sepsis (35%). In contrast to induction, platelet recovery was notably delayed during consolidation cycles. The overall response rate (complete remission [CR]/CR with incomplete count recovery) was 72%; it was 97% in de novo AML and was 43% in secondary AML. During the venetoclax prephase, marrow blast reductions (≥ 50%) were noted in NPM1-, IDH2-, and SRSF2-mutant AML. Venetoclax combined with 5 + 2 induction chemotherapy was safe and tolerable in fit older patients with AML. Although the optimal postremission therapy remains to be determined, the high remission rate in de novo AML warrants additional investigation (ANZ Clinical Trial Registry No. ACTRN12616000445471).
URI: http://ahro.austin.org.au/austinjspui/handle/1/23861
DOI: 10.1200/JCO.20.00572
ORCID: 0000-0001-5773-103X
PubMed URL: 32687450
Type: Journal Article
Appears in Collections:Journal articles

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