For patients older than 65 years with newly diagnosed acute myeloid leukemia (AML) who were ineligible for standard induction therapy, adding the investigational pan-histone deacetylase (pan-HDAC) inhibitor pracinostat to azacitidine resulted in better complete remission and overall survival rates than azacitidine alone, results of a multicenter phase 2 trial showed.
Among 50 patients treated with the combination, 26 (52%) achieved the primary endpoint of either a complete remission (CR), CR with incomplete recovery of blood counts (CRi), or morphologic leukemia-free state (MLFS).
The median overall survival (OS) was 19.1 months, which compares favorably with historical data on similar patients treated with single-agent azacitidine, reported, from the University of Texas MD Anderson Cancer Center in Houston and his colleagues.
“[T]his study shows that pracinostat in combination with azacitidine has the potential to be a safe and effective regimen in the frontline treatment of older patients with AML unfit for [induction chemotherapy],” they wrote in.
Pracinostat is an oral pan-HDAC inhibitor that has been shown to have modest activity against AML as a single agent, but synergistic activity when combined with hypomethylating agent azacitidine, a standard of care for older patients with AML in the.
The investigators enrolled 50 patients with a median age of 75 years (range, 66-84 years). The cohort included 33 patients with de novo AML, 12 with AML secondary to myelodysplasia syndrome or myleoproliferative neoplasia, and five with therapy-related AML.
The patients were treated with pracinostat 60 mg daily for 3 days each week for 3 consecutive weeks in addition to azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle.
As noted, 26 patients reached the clinical endpoint, including 21 with a CR, 2 with a CRi, and 3 with MLFS. Additionally, two patients had a partial response (PR) and four had a PR with incomplete recovery of blood counts.
The median OS was 19.1 months, and the median progression-free survival (PFS) was 12.6 months. The 1-year OS rate was 62%. The 60-day mortality rate was 10%.
The authors noted that the survival data were superior to those seen in the phase 3, which compared azacitidine therapy with conventional regimens in patients older than 65 years with newly diagnosed AML who were not eligible for stem cell transplants. In that trial, median OS was 10.4 months, the CR rate was 19.5% (vs. 49% in the present study), the 1-year OS rate was 46.5%, and the 60-day mortality rate was 16.2%.
They acknowledged, however, that the validity of the comparison is limited by their study’s small sample size, potential differences between the study populations, and lack of a control group in the present study. The investigators also found that clearance rates of baseline somatic mutations correlated with response to treatment.
Grade 3 or greater treatment-emergent adverse events occurred in 43 of the 50 patients, including infections, thrombocytopenias, and febrile neutropenias.
“On the basis of these encouraging results, a phase 3, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine () is currently ongoing to confirm superiority of the combination in this difficult-to-treat AML population,” the investigators wrote.
The study was supported by research funding from MEI Pharma, which helped develop pracinostat. Dr. Garcia-Manero reported having no disclosures. Multiple coauthors reported financial relationships with MEI and others. One coauthor is an MEI employee.
SOURCE: Garcia-Manero G et al. .