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Predicting Response to Venetoclax Combination Therapy in Resistant AML

By: Kelly M. Hennessey, PhD
Posted: Wednesday, April 7, 2021

Aaron D. Goldberg, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues analyzed data on patients with relapsed or refractory acute myeloid leukemia (AML) treated with venetoclax combination therapies. They found that those receiving the combination of azacitidine plus venetoclax achieved the highest response rate. In addition, NPM1 mutations were associated with better outcomes, whereas mutations in TP53, KRAS/NRAS, and SF3B1 were linked to poorer outcomes. Their results were published in Blood Advances.

This retrospective study included 86 patients with relapsed or refractory AML who received venetoclax combination therapy. Patients were administered azacitidine plus venetoclax (n = 35), decitabine plus venetoclax (n = 20), low-dose cytarabine plus venetoclax (n = 27), or sequential therapy (n = 4). Of the 15 patients who received subsequent allogeneic stem cell transplantation, 10 patients were treated with azacitidine plus venetoclax, 4 patients were treated with decitabine plus venetoclax, and 1 patient received low-dose cytarabine plus venetoclax.

The overall response rate was 31% (n = 27), with 24% (n = 21) reaching complete remission or complete remission with incomplete hematologic recovery, and 7% (n = 6) achieving a morphologic leukemia-free state. Of the patients with an overall response, 45% relapsed after venetoclax therapy. The median duration of response was 7.8 months, with a median follow-up of 12 months. After ending venetoclax therapy, the median overall survival dropped to 2.5 months.

The differences in overall survival seemed to be associated with the type of venetoclax combination treatment. Patients treated with azacitidine plus venetoclax had an overall survival of 25 months, compared with 5.4 months and 3.9 months with decitabine plus venetoclax and low dose cytarabine plus venetoclax, respectively.

Additionally, the study authors noted the findings based on clinical and molecular predictors of outcomes. “NPM1 mutations predicted higher response rates; adverse-risk cytogenetics and mutations in TP53, KRAS/NRAS, and SF3B1 predicted worse overall survival,” they stated.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.


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