Chapter 7 154 Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/ or BIM Setup Between April 2017 and September 2018, patients with Secondary Acute Myeloid Leukemia (sAML) received venetoclax within a named patient program in Salzburg, Austria. Efficacy and safety data were retrospectively collected. There is no information available on funding or ethics approval. Patients signed an informed consent for the use of venetoclax and to allow for collection of personal data. Patients The expanded access program was open to patients with secondary acute myeloid leukemia, meaning that patients developed AML either from an antecedent hematological malignancy. Seven patients were treated and included in the analysis population. Patients had a median age of 74 years (range, 65-82). Four patients had prior myelodysplastic syndrome (MDS), two patient developed leukemic transformation based on chronic myeloproliferative neoplasms, and one patient suffered from antecedent chronic myelomonocytic leukemia. Interventions Patients received venetoclax, a B-cell leukemia/lymphoma-2 (BCL2) inhibitor. After a stepwise ramp-up of venetoclax dosing, all seven patients received venetoclax daily at a dose of 800 mg. In four patients there was no dose modification, two patients received an intermittent 200 mg dose, and one patient had a temporary interruption. Outcome Progression-free survival (PFS), overall survival (OS), mutation status, BLC-2/BIM expression and toxicity were evaluated. Median OS from venetoclax initiation was 55 days (range, 15-549). One patient with antecedent MDS and one with antecedent myeloproliferative neoplasm achieved a complete remission with a PFS of 505 and 352 days, respectively. Another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. High BCL-2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with OS.
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