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Venetoclax Plus Cladribine and Low-Dose Cytarabine Alternating With Azacitidine and Venetoclax in Newly Diagnosed Older or Unfit Patients With AML


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In a single-institution phase II study reported in the Journal of Clinical Oncology, Tapan M. Kadia, MD, and colleagues found that venetoclax and a lower-intensity backbone of cladribine and low-dose cytarabine alternating with azacitidine and venetoclax resulted in a high response rate in older patients or patients unfit for intensive therapy with newly diagnosed acute myeloid leukemia (AML).

Tapan M. Kadia, MD

Tapan M. Kadia, MD

The study included 60 patients aged ≥ 60 years or unfit for intensive therapy enrolled at The University of Texas MD Anderson Cancer Center between November 2018 and February 2021. Induction and the first consolidation course consisted of cladribine/low-dose cytarabine and venetoclax. The next two consolidation courses consisted of azacitidine, with subsequent courses alternating between two courses of cladribine/low-dose cytarabine plus venetoclax and two of azacitidine plus venetoclax.  The primary outcome measure was the rate of composite complete response, consisting of complete response plus complete response with incomplete blood count recovery.

Key Findings

Complete response or complete response with incomplete blood count recovery was observed in 56 of 60 patients (93%, 95% confidence interval [CI] = 83%–98%), with complete response in 48 (80%). Median duration of response was not reached (95% CI = not estimable–not estimable), with estimated 12- and 24-month durations for 82.8% and 75.9% of responses. Among 51 responders with available data, 43 (84%) were negative for measurable residual disease.

At a median follow-up of 22.1 months, median disease-free survival was not reached (95% CI = 19.6 months–not estimable), with estimated 12- and 24-month rates of 71.0% and 60.5%. Median overall survival was not reached (95% CI = 25.4 months–not estimable), with estimated 12- and 24-month rates of 72.9% and 63.5%.

The most common grade 3 or 4 nonhematologic adverse events were febrile neutropenia (55%) and pneumonia (23%). Grade 4 tumor lysis syndrome occurred in one patient. Death within 4 weeks occurred in one patient, due to pneumonia.

The investigators concluded, “Venetoclax and [cladribine/low-dose cytarabine] alternating with venetoclax and azacitidine is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and disease-free survival are encouraging. Further study of this non–anthracycline-containing backbone in younger patients unfit for intensive chemotherapy, as well as comparisons to standard front-line therapies, is warranted.”

Dr. Kadia, of the Department of Leukemia, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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