Clinical Experience With Ibrutinib Alone or in Combination With Either Cytarabine or Azacitidine in Patients With Acute Myeloid Leukemia

Preclinical studies have suggested that ibrutinib may have a clinical benefit in acute myeloid leukemia (AML). Treatment with ibrutinib alone or in combination with cytarabine or azacitidine was evaluated in 36 patients with AML. The study was terminated because of limited efficacy. Safety was consistent with established safety profiles of the individual drugs. The potential utility of ibrutinib in AML remains uncertain. Background: Preclinical studies have suggested a role for Bruton tyrosine kinase (BTK) as a potential therapeutic target in acute myeloid leukemia (AML), and anti-AML activity in vivo has been demonstrated with BTK inhibitors. Patients and Methods: In this open-label phase 2a study, patients with AML were treated with ibrutinib 560 mg per day alone (cohort 1; n = 7), or ibrutinib in combination with either cytarabine 20 mg administered subcutaneously twice daily for 10 days of a 28-day cycle (cohort 2; n = 21) or azacitidine 75 mg/m(2) administered intravenously once daily on days 1 to 7 of a 28-day cycle (cohort 3; n = 8). Best overall response (primary end point), overall survival, and safety were summarized. Results: A total of 36 patients were enrolled and received treatment; median duration of ibrutinib treatment was 5.4 weeks, and median time on study was 16 months. Of 24 patients evaluable for response, 1 partial remission (cohort 3) and 1 complete remission (cohort 2) were observed; the remaining responses were treatment failures. Median overall survival was 4.0 months in cohort 1, 2.2 months in cohort 2, 2.8 months in cohort 3, and 2.4 months for the overall population. No unexpected safety signals were identified. Grade 3 or higher adverse events that occurred in >= 10% of patients included AML progression, febrile neutropenia, pneumonia, anemia, thrombocytopenia, fatigue, asthenia, and respiratory failure. Conclusion: Ibrutinib alone or in combination with cytarabine or azacitidine demonstrated an acceptable safety profile. However, limited efficacy with ibrutinib was observed in patients with AML.