Introduction: Acute myeloid leukemia (AML) is a heterogeneous disease that can express more than one phenotypically distinct clone at diagnosis and during its evolution. Venetoclax, a BCL-2 inhibitor, along with azacitidine has been proposed as a therapeutic option. There are reports suggesting that people with AML and monocytic phenotype may experience resistance to venetoclax, although this has not been confirmed in a population of patients who are candidates for intensive treatment.

Patients and methods: In this retrospective, single-center study, we evaluated responses with low-dose venetoclax with itraconazole and azacitidine (Aza-Ven) in adults with AML according to their immunophenotype and compared them to a historical cohort from the intensive chemotherapy era. The primary outcome was the response at the end of induction. Secondary outcomes were event-free survival and overall survival.

Results: 92 patients were included from January 2017 to April 2024, with a median age of 46 years. Thirty-six patients received first-line Aza-Ven, of whom 27.8% had a monocytic phenotype (n=10) and 72.2% other phenotypes (n=26). In patients who received Aza-Ven , the response at the end of induction was 30% vs. 53.8% in patients with monocytic phenotype vs. others, respectively (p=.18). Median OS for monocytic patients was 6.4 months vs. 10.9 months for other phenotypes (p=.171); median DFS was 2.4 months vs. 5.2 months, respectively (p=.075)

In the historical cohort of 46 patients who started intensive chemotherapy, 20 patients had monocytic phenotype. Complete response was observed in 61.9% of patients with this phenotype vs. 42.9% in other phenotypes (p=0.297). The mean OS for patients with monocytic phenotype was 7.1 vs 9.3 months in other phenotypes (p.803). The median DFS was 4.8 months vs. 2.6 months, respectively (p=.929). OS 9.2 months in patients with monocytic phenotype compared to 6.54 and 12.1 months in patients with other phenotypes.

In the Cox regression model, age for all patients was associated with an increased risk of the event (HR 1.02 95% CI 1-1.04), while use of Aza-Ven decreased the risk of the event (HR 0l.508 95% CI 0.276-0.936). When separated by treatment groups, only age was predictive of OS in the intensive QT group (HR 1.02 (95% CI 1-1.04), but not the phenotype.

Conclusion: Patients with monocytic phenotype experienced higher rates of refractoriness and worse outcomes, although no statistical significance was obtained in this small sample. It´s imperative to analyze prospective trials involving the use of venetoclax-based regimens in patients with this monocytic phenotype, in light of previous reports and the findings in this single-center study, seeking to optimize therapy in this population

Disclosures

Gomez-Almaguer:Amgen: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Advisory board, Speakers Bureau; Novartis: Consultancy, Other: Advisory board, Speakers Bureau; Takeda: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; BMS: Consultancy, Other: Advisory board, Speakers Bureau; Tevas: Speakers Bureau; AbbVie: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Sanofi: Speakers Bureau; Seattle Genetics: Research Funding; Astex Pharmaceuticals: Research Funding; Incyte: Research Funding; Blueprint Medicines: Research Funding; Kartos Therapeutics: Research Funding; Gilead/Forty Seven: Research Funding; ConstellationPharmaceuticals: Research Funding. Gomez-De Leon:Amgen: Honoraria; bms: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Sanofi: Honoraria, Other: Advisory board; Janssen: Other: Advisory board; Abbvie: Honoraria.

Off Label Disclosure:

Use of low dose venetoclax (100 mg) fixed dose with an azole to potenciate its effect

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2024
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