Single-center experience with venetoclax combinations in patients with newly diagnosed and relapsed AML evolving from MPNs

Abstract

In patients with acute myeloid leukemia evolving from myeloproliferative neoplasms (post-MPN-AML), the clinical activity of the B-cell lymphoma 2 inhibitor venetoclax remains to be determined. We review our experience with venetoclax-based regimens in 14 newly diagnosed (frontline [FL]) and 17 relapsed/refractory (R/R) post-MPN-AML patients. Venetoclax was used in combination with hypomethylating agents in 58% of cases and in 19% with intensive chemotherapy (treatment including cytarabine ≥1 g/m2 or CPX-351); the remaining patients received cladribine and low-dose cytarabine or isocitrate dehydrogenase 1/2 inhibitors. The median dose of venetoclax during the initial cycle was 100 mg in all patients (range, 50-800 mg) and 200 mg (range, 100-800 mg) for FL patients. The venetoclax dose was adjusted when used concomitantly with azole antifungal agents. In FL patients, complete remission with and without count recovery in 6 patients (median duration of 6.4 months) and partial remission in 1 patient was noted, with a median overall survival of 7 months. In R/R patients, no formal responses were seen, with a median overall survival of 3 months. Hematologic toxicities and adverse events were frequent; 83% of patients developed grade 3 or higher infection during the initial cycle. Severe hemorrhagic complications were observed in 14 patients, including 6 cases of intracranial and subdural hemorrhage. Overall 4-week and 8-week mortality were 10% and 32%, respectively. Given the substantial treatment-associated hematologic toxicity and mortality, and modest short-lived responses only in newly diagnosed patients with venetoclax-based regimens, additional treatment options are urgently needed for these patients.

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