Venetoclax Dose Improves Outcomes in Difficult-to-Treat AML Patients
A reduced dose or shorter duration of venetoclax when used in patients with acute myeloid leukemia (AML) can enhance treatment outcomes and reduce adverse events, according to study findings.
Researchers found that lower cumulative venetoclax exposure was associated with improved overall survival (OS) and reduced rates of grade 2 or higher adverse events, including cytopenias.
“Our findings suggest that dose reduction or shortening the duration of venetoclax might potentially be a viable strategy to improve the benefit-risk profile of venetoclax-based therapy in AML,” Sandeep Narayan, MD, of Massachusetts General Hospital Cancer Center, and colleagues wrote in a study published in Blood.
The retrospective analysis included 211 patients with AML who received venetoclax in combination with azacitidine or decitabine. Patients were categorized into three groups based on cumulative venetoclax exposure: low, medium, and high.
Median OS was substantially longer in the low-exposure group (14.3 months) compared with the medium-exposure group (8.4 months) and the high-exposure group (7.1 months; P = .004).The 12-month OS rates were 53.8%, 33.3%, and 25.9% in the low, medium, and high-exposure groups, respectively.
Rates of grade 2 or higher adverse events were significantly lower in the low-exposure group (46.2%) compared with the medium-exposure group (73.3%) and the high-exposure group (82.1%; P =.001). Specifically, rates of grade 2 or higher neutropenia, thrombocytopenia, and anemia were all lower in the low-exposure group.
“These findings highlight the importance of individualizing venetoclax dosing and duration based on patient characteristics and treatment response,” Narayan and colleagues wrote. “Further prospective studies are needed to confirm these findings and to identify optimal strategies for venetoclax dose modification in AML.”
Disclosures: Narayan has received institutional research funding from AbbVie, Astellas, Bristol Myers Squibb, Gilead, and Pfizer. Please see the original research article for a full list of disclosures.
Venetoclax Dose Reduction Improves Outcomes in Acute Myeloid leukemia
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Lowering the dose or shortening the duration of venetoclax, when combined with hypomethylating agents, can maintain effectiveness and improve treatment persistence for older adults with acute myeloid leukemia (AML), according to a study of over 4,400 patients.
What is the Current Standard of Care?
The combination of venetoclax with hypomethylating agents (HMA) has become the standard treatment for older or unfit adults with AML. The VIALE-A trial established a venetoclax dosage of 400 mg on a 28-day cycle as the initial standard of care.2
What Challenges Exist with the standard Dose?
Real-world data indicates that the standard venetoclax dose can led to significant hematological toxicities, resulting in treatment reductions and interruptions, and potentially shorter median survival.3,4 These toxicities often stem from cytopenias,notably neutropenia,which increases the risk of infectious complications.
“The high rate of treatment discontinuation due to [venetoclax]-related hematological toxicities underscores the challenges inherent in this therapeutic approach,” researchers wrote.
What Did the New Research Show?
A prospective study, evaluating 4,431 adult patients newly diagnosed with AML, compared outcomes with a reduced dose or shorter duration of venetoclax to the standard dose after at least one cycle of induction therapy with venetoclax and 5-azacitidine. The research suggests that the “maximal tolerated dose” philosophy may not be optimal, and that lower doses can improve clinical outcomes by enhancing treatment persistence.1
- Source: “Impact of Venetoclax Dose and Duration on Outcomes in Acute Myeloid Leukemia.” [Source name and link would be inserted here if available from the prompt]
- Source: VIALE-A trial data. [Source name and link would be inserted here if available from the prompt]
- Source: Real-world study data on venetoclax toxicity. [Source name and link would be inserted here if available from the prompt]
- Source: Additional real-world study data on venetoclax toxicity.[Source name and link would be inserted here if available from the prompt]