Abstract
We evaluated response to venetoclax/hypomethylating agents (HMA) in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease. The median age of these patients was 65 years (range, 19-81). The patients had a median of two sites of extramedullary disease (range, 1-5) and 35 (76%) had concurrent bone marrow involvement. Twenty (43%) patients had high-risk genetic features according to the European LeukemiaNet 2022 classification. Twenty-nine (63%) had relapsed or were refractory after intensive chemotherapy, including 13 (28%) who had undergone prior allogeneic hematopoietic cell transplantation. Patients received a median of two cycles of venetoclax/HMA (range, 1-31). Twenty (43%) patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) after venetoclax/HMA and five (11%) achieved a partial remission (PR). Six patients were subsequently consolidated with allogeneic hematopoietic cell transplantation (CR/CRi, N=4; PR, N=2). The median follow-up was 49.1 months (95% confidence interval [95% CI]: 26.1 months - not reached) and the median overall survival was 6.4 months (95% CI: 5.1-11 months). One-year and 2-year overall survival rates were 29.3% (95% CI: 18.6-46.2%) and 12.3% (95% CI: 5.5-27.6%), respectively. Age, with a cutoff of 60 years, did not have an impact on overall survival (P=0.90). Relapse occurred in 12 of 20 (60%) patients who achieved CR/CRi after venetoclax/ HMA treatment. Of those, all except one succumbed to their disease. Six (30%) patients were in CR/CRi at last follow-up and two (10%) died in CR. In our cohort of patients with AML with extramedullary disease with high-risk features, treatment with venetoclax/HMA resulted in an encouraging overall response rate of 54% with a CR/CRi rate of 43.5%. However, venetoclax/ HMA alone may not be effective in maintaining disease control.