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Ref Type Journal Article
PMID (30361262)
Authors DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A
Title Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia.
Journal Blood
Vol 133
Issue 1
Date 2019 Jan 03
URL
Abstract Text Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N = 145) were at least 65 years old with treatment-naive AML and were ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1-5, intravenously [IV]) or azacitidine (75 mg/m2, days 1-7, IV or subcutaneously). In the expansion, 400 or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR + CRi rate of 73% in the venetoclax 400 mg + HMA cohort. Patients with poor-risk cytogenetics and those at least 75 years old had CR + CRi rates of 60% and 65%, respectively. The median duration of CR + CRi (all patients) was 11.3 months, and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (This trial was registered at www.clinicaltrials.gov as #NCT02203773).

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown acute myeloid leukemia not applicable Azacitidine + Venetoclax FDA approved Actionable In a Phase I/II trial that supported FDA approval, Venclexta (venetoclax) in combination with decitabine or azacitidine resulted in complete remission or complete remission with incomplete count recovery in 65% (40/62) of patients 75 years old or older with treatment-naive acute myeloid leukemia ineligible for intensive chemotherapy, with an overall survival of 11 months (PMID: 30361262; NCT02203773). detail... 30361262
Unknown unknown acute myeloid leukemia not applicable Decitabine + Venetoclax FDA approved Actionable In a Phase I/II trial that supported FDA approval, Venclexta (venetoclax) in combination with decitabine or azacitidine resulted in complete remission or complete remission with incomplete count recovery in 65% (40/62) of patients 75 years old or older with treatment-naive acute myeloid leukemia ineligible for intensive chemotherapy, with an overall survival of 11 months (PMID: 30361262; NCT02203773). detail... 30361262