Combined with chemotherapy, venetoclax appears to be effective for treating acute myeloid leukemia (AML) among fit elderly patients, according to research from a phase 1b trial published in the Journal of Clinical Oncology.

Previous research indicated that, when combined with low-dose cytarabine (LDAC), venetoclax, a B-cell lymphoma 2 inhibitor, yields an overall response rate (ORR) of more than 50% in elderly patients with AML who are unfit for intensive chemotherapy. Whether intensive chemotherapy may be combined with venetoclax among fit patients with AML is unknown.

A team of researchers conducted an open-label, phase 1b, dose-escalation study phase 1b CAVEAT trial (ANZ Clinical Trial Registry Number: ACTRN12616000445471) to evaluate the safety and efficacy of escalated doses of venetoclax, combined with a 5 + 2 chemotherapy regimen, among fit elderly patients with AML. Patients aged 65 years or older, or 60 years or older with monosomal karyotype, were eligible.

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Overall, 51 patients were included, among whom the median age was 72 years (range, 6380), 33 (65%) were men, 28 (55%) had de novo disease, 12 (24%) had a TP53 mutation. All patients had an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

There were 5 cohorts representing escalating doses of venetoclax: 50 mg per day (A; 8 patients), 100 mg (B; 8 patients), 200 mg (C; 9 patients), 400 mg (D; 8 patients), and 600 mg (E; 18 patients). The maximum tolerated dose was not reached.

The ORR, defined as complete remission or complete remission with incomplete count recovery, was 72% overall, with an ORR of 97% in patients with de novo disease vs 43% in patients with secondary AML. Patients with de novo AML had longer overall survival rates compared with patients with secondary AML. In addition, patients with TP53 mutations had poor clinical outcomes, with a median overall survival of 3.6 months, compared with 11.2 months in the overall cohort.

The most common grade 3 or worse nonhematologic adverse events during induction were febrile neutropenia (55%) and sepsis (35%).

“In conclusion, venetoclax in combination with modified intensive induction is tolerable in fit older patients with newly diagnosed AML and paves the way for future investigation of venetoclax in combination with intensive chemotherapy in younger patients with AML,” the authors wrote.


Chua CC, Roberts AW, Reynolds J, et al. Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (CAVEAT): a phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy. J Clin Oncol. Published online July 22, 2020. doi:10.1200/JCO.20.00572