Venetoclax combination therapy in relapsed/refractory acute myeloid leukemia: A single institution experience. (March 2020)

• Record Type: Journal Article
• Authors: Gaut, Daria; Burkenroad, Aaron; Duong, Tuyen; Feammelli, Jesse; Sasine, Joshua; Schiller, Gary
• Is Part Of: Leukemia research. Volume 90(2020)
• Publication Date: 2020-03
• Subjects: AML acute myeloid leukemia -- ANC absolute neutrophil count -- BCL-2 b-cell lymphoma 2 -- CR complete remission -- CRi complete remission with incomplete hematologic recovery -- CTCAE common terminology criteria for adverse events -- ECOG eastern cooperative oncology group -- ELN European LeukemiaNet -- FLT3 Fms-like tyrosine kinase 3 -- G-CSF granulocyte colony-stimulating factor -- HMA hypomethylating agent -- IDH2 isocitrate dehydrogenase 2 -- LDAC low-dose cytarabine -- MRSA methicillin-resistant Staphylococcus aureus -- NPM1 nucleophosmin 1 -- ORR objective response rate -- OS overall survival -- PR partial remission -- PFS progression-free survival -- RBC red blood cell -- RUNX1 runt-related transcription factor 1 -- TP53 tumor protein 53 -- VEN venetoclax; Acute myeloid leukemia -- Relapsed/refractory -- Venetoclax -- Objective response rate -- Progression-free survival; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2020.106314
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: 14 relapsed/refractory AML patients treated with VEN combination therapy. Objective response rate was 35.7%. Median overall survival was 4.7 months. No difference in response if prior stem cell transplant or HMA exposure. Adverse effects from pre-existing bone marrow failure, exacerbated by treatment. Abstract: Venetoclax (VEN) is a selective BCL-2 inhibitor that has been shown to be effective when used in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) for treatment-naïve, elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Data on its use in the relapsed/refractory setting are limited. A retrospective analysis was performed among 14 patients with relapsed or refractory AML treated with VEN combination therapy at the University of California Los Angeles from 2018-2019. Eight patients received VEN in combination with azacitidine, 5 patients with decitabine, and 1 patient with LDAC. The majority (10 patients, 71.4%) had adverse cytogenetics. Three patients (21.4%) had undergone an allogeneic stem cell transplant prior to VEN therapy, and 5 patients (35.7%) had leukemia that failed HMA therapy prior. The objective response rate (ORR) was 35.7% (3 patients achieved complete remission with incomplete hematologic recovery and 2 patients achieved partial remission). Three patients (21.4%) were successfully transitioned to either allogeneic bone marrow transplant (2 patients) or donor lymphocyte infusion (1 patient). Seven patients (50.0%) developed a grade 3 or greater infection following VEN therapy, and 3 patients (21.4%) developed a grade 3 or greater intracranial hemorrhage. Three patients experienced early death within 30 days of therapy (2 from infection, 1 from bleeding). The median overall survival (OS) was 4.7 months, and the 1-year OS rate was 23.6% (95% CI 4.4–51.2) for the entire patient cohort. Overall, the response rate was not inferior to that with conventional salvage chemotherapy, but there were notable complications as a result of prolonged cytopenias.