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

Guillermo Garcia-Manero*, Yasmin Abaza, Koichi Takahashi, Bruno C. Medeiros, Martha Arellano, Samer K. Khaled, Mrinal Patnaik, Olatoyosi Odenike, Hamid Sayar, Mohan Tummala, Prapti Patel, Lori Maness-Harris, Robert Stuart, Elie Traer, Kasra Karamlou, Abdulraheem Yacoub, Richard Ghalie, Ruben Giorgino, Ehab Atallah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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 patientswhowere 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 75mg/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 therapyrelated 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 as #NCT01912274.

Original languageEnglish (US)
Pages (from-to)508-518
Number of pages11
JournalBlood Advances
Issue number4
StatePublished - Feb 26 2019

ASJC Scopus subject areas

  • Hematology


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