The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Adding venetoclax to treatment with low-intensity chemotherapy (LIC) and a FLT3 inhibitor can improve outcomes in older patients with FLT3-mutated acute myeloid leukemia (AML), a new study suggests.

Results from this retrospective study were presented at the 2021 American Society of Hematology (ASH) Annual Meeting by Musa Yilmaz, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Dr Yilmaz and colleagues reviewed records of patients with newly diagnosed FLT3-mutated AML who participated in LIC clinical trials between 2012 and 2021. The researchers compared outcomes between patients who received triplet therapy with LIC, venetoclax, and a FLT3 inhibitor (n=27) and patients who received doublet therapy with LIC and a FLT3 inhibitor (n=60).

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The median age was 69 years (range, 40-85 years) in the triplet cohort and 71 years (range, 51-83 years) in the doublet cohort. AML was de novo in 74% and 71% of patients, respectively.

In the triplet cohort, LIC consisted of a hypomethylating agent (HMA) in 100% of patients. All patients in this cohort also received venetoclax. The FLT3 inhibitors patients received were gilteritinib (44%), sorafenib (37%), quizartinib (15%), and midostaurin (4%).

In the doublet cohort, LIC consisted of an HMA (83%) or low-dose cytarabine alone or with cladribine (17%). The FLT3 inhibitors used were sorafenib (60%), quizartinib (27%), and midostaurin (13%).


Response rates were significantly higher with triplet therapy. The rate of complete response (CR) was 67% with triplet and 32% with doublet therapy (P <.01). The rate of CR with incomplete count recovery was 93% and 70%, respectively (P =.02).

The rate of FLT3 polymerase chain reaction negativity was 96% with triplet and 54% with doublet therapy (P <.01). The rate of multicolor flow cytometry negativity was 83% and 38%, respectively (P <.01).

The median number of cycles to achieve the best response was 1 (range, 1-4) for the triplet group and 2 (range, 1-5) for the doublet group.

The median time to neutrophil recovery was 42 days in the triplet group and 21 days in the doublet group (P =.075). The median time to platelet recovery was 29 days and 35 days, respectively (P =.20).

The 60-day mortality rates were similar between the triplet group and the doublet group — 7% and 10%, respectively.

However, overall survival (OS) was superior in the triplet group. The 2-year OS rate was 70% in the triplet cohort and 22% in the doublet cohort.

The median OS was not reached in the triplet cohort, was 15.7 months for patients in the doublet cohort who received a second-generation FLT3 inhibitor, and was 8.7 months for those in the doublet cohort who received a first-generation FLT3 inhibitor (P =.006).

When patients were stratified by stem cell transplant, there was no significant difference in OS for patients in the triplet cohort (P =.818). In the doublet cohort, transplant was associated with improved OS (P =.016).

Dr Yilmaz said these findings “are promising,” but they should be validated prospectively, ideally in a randomized trial.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.


Yilmaz M, Kantarjian H, Short NJ, et al. Hypomethylating agent (HMA) therapy and venetoclax (VEN) with FLT3 inhibitor “triplet” therapy is highly active in older/unfit patients with FLT3 mutated AML. Presented at ASH 2021; December 11-14, 2021. Abstract 798.