Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study

• Type of Material: Article
• Authors: Guillermo Garcia-Manero, University of Texas MD Anderson Cancer Center; Yasmin Abaza, University of Texas MD Anderson Cancer Center; Koichi Takahashi, University of Texas MD Anderson Cancer Center; Bruno C. Medeiros, Stanford University; Martha Arellano, Emory University; Samer K. Khaled, City of Hope; Mrinal Patnaik, Mayo Clinic; Olatoyosi Odenike, University of Chicago; Hamid Sayar, Indiana University; Mohan Tummala, Mercy Hospital; Prapti Patel, University of Texas Southwestern; Lori Maness-Harris, University of Nebraska; Robert Stuart, Medical University of South Carolina; Elie Traer, Oregon Health and Science University; Kasra Karamlou, Arizona Oncology; Abdulraheem Yacoub, University of Kansas Cancer Center; Richard Ghalie, MEI Pharma, Inc; Ruben Giorgino, Helsinn Healthcare SA; Ehab Atallah, Medical College of Wisconsin
• Language: English
• Date: 2019-02-26
• Publisher: American Society of Hematology: Blood Advances
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by The American Society of Hematology.
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2018027409
• Title of Journal or Parent Work: Blood Advances
• ISSN: 2473-9529
• Volume: 3
• Issue: 4
• Start Page: 508
• End Page: 518
• Grant/Funding Information: This study was supported by research funding from MEI Pharma Inc.; This study was developed jointly by the sponsor and investigators.
• Keywords: age; OS rate; azacitidine; AML; pracinostat; treatment; CR rate
• Research Categories: Health Sciences, Oncology; Chemistry, Pharmaceutical; Health Sciences, Medicine and Surgery

Abstract

Pracinostat, a potent oral pan-histone deacetylase inhibitor with modest single-agent activity in acute myeloid leukemia (AML), has shown synergistic antitumor activity when combined with azacitidine. This single-group, multicenter phase 2 study assessed the safety and efficacy of pracinostat combined with azacitidine in patients who were at least 65 years old with newly diagnosed AML and who were ineligible for standard induction chemotherapy. Patients received pracinostat 60 mg/d, 3 d/wk, for 3 consecutive weeks, plus azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle. Primary endpoints were complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS) rates of the combination. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS) of the regimen. Fifty patients (33 de novo, 12 secondary, and 5 therapy-related AML) were enrolled. Twenty-six patients (52%) achieved the primary endpoint of CR (42%), CRi (4%), and MLFS (6%). Median OS and PFS were 19.1 months (95% confidence interval [CI], 10-26.5 months) and 12.6 months (95% CI, 10-17.7 months), respectively, with a 1-year OS rate of 62%. Forty-three patients (86%) experienced at least 1 grade 3 or worse treatment-emergent adverse event with the combination, with infections (52%), thrombocytopenia (46%), and febrile neutropenia (44%) reported as the most common toxicities. The 30- and 60-day all-cause mortality rates were 2% and 10%, respectively. DNA sequencing revealed somatic mutations at baseline, and clearance rates correlated with response to treatment. Pracinostat plus azacitidine is a well-tolerated and active regimen in the frontline treatment of older patients with AML unfit for intensive therapy. A larger controlled trial is ongoing. This trial was registered at www.clinicaltrials.gov as #NCT01912274.