(230) Time is of the Essence: Reduced Venetoclax Duration in Patients with Acute Myeloid Leukemia

Poster Abstract:

Background:
Venetoclax (VEN), combined with a hypomethylating agent (HMA) like azacitidine or decitabine, demonstrates high rates of complete remission for unfit patients with newly diagnosed acute myeloid leukemia (AML), and is the current standard of care for treatment in this patient population. However, tolerability to this regimen varies, and many patients experience delays in subsequent treatment cycles due to hematologic toxicity, necessitating shortened days of VEN administration and extended cycle lengths.
AML is increasingly being characterized by distinct molecular subtypes such as secondary ontogeny in addition to TP53 mutations, and there is interest in differences in outcomes resulting from these molecular differences. Prior studies report shorter durations of HMA+VEN lead to similar efficacy with reduced toxicities. However, it is unknown if patients with distinct molecular subtypes tolerate HMA+VEN differently and if this affects treatment outcomes. Therefore, there is a clear need to investigate if these distinct molecular subtypes lead to delayed treatment and worse outcomes.

Objectives:
This study aims to determine whether secondary ontogeny mutations affect HMA+VEN cycle length and days of venetoclax administered within each cycle.

Methods:
This is a single-center, retrospective, observational study including patients 18 years and older at Dana-Farber Cancer Center with newly diagnosed AML receiving at least one cycle of HMA+VEN and had genetic sequencing between March 1, 2016 – March 30, 2022. Patients were excluded if they did not achieve a morphological leukemia-free state or better response to treatment, or if the venetoclax duration could not be determined for at least one cycle. Primary endpoints include HMA+VEN treatment cycle length, days of VEN administration per cycle, and time to hematologic recovery per cycle. Secondary endpoints include proportion of patients proceeding to transplant, proportion of MRD negative disease, and relapse rate. Safety endpoints include composite hospitalizations, incidence of febrile neutropenia, and number of blood and platelet transfusions per cycle. Patients will be separated into three groups based on the presence of a TP53 mutation (“TP53 group”), presence of one or more secondary ontogeny mutations not including TP53 mutation (“secondary group”) and all other patients (“de novo group”). Descriptive statistics will be used to characterize primary, secondary, and safety endpoints. Inferential statistics will be used to compare endpoints between de novo, TP53, and secondary ontogeny groups.
Results/Discussion/Conclusions forthcoming.

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