Journal
BLOOD ADVANCES
Volume 5, Issue 8, Pages 2156-2164Publisher
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DOI: 10.1182/bloodadvances.2020003934
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Funding
- Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health [P30 CA016672]
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In patients with acute myeloid leukemia evolving from myeloproliferative neoplasms, the clinical activity of the B-cell lymphoma 2 inhibitor venetoclax remains to be determined. Venetoclax-based regimens showed modest short-lived responses in newly diagnosed patients, while no formal responses were seen in relapsed/refractory patients. However, significant treatment-associated hematologic toxicity and mortality were observed, highlighting the urgent need for additional treatment options for these patients.
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 3 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. Venetodax was used in combination with hypomethylating agents in 58% of cases and in 19% with intensive chemotherapy (treatment including cytarabine >= 1 g/m(2) or CPX-351); the remaining patients received dadribine and low-dose cytarabine or isocitrate dehydrogenase 1/2 inhibitors. The median dose of venetodax 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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