Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy
Jörge E. Cortes, Florian H. Heidel, Walter Fiedler, Benjamin D. Smith, Tadeusz Robak, Pau Montesinos, Anna Candoni, Brian Leber, Mikkael A. Sekeres, Daniel A. Pollyea, Roxanne Ferdinand, Weidong Wendy, Thomas O’Brien, Ashleigh O’Connell, Geoffrey Chan, Michael Heuser
Abstract
BACKGROUND: The phase 2 BRIGHT AML 1003 trial evaluated efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized patients to receive glasdegib + LDAC (n = 78) or LDAC alone (n = 38). The rate of complete remission (CR) was 19.2% in the glasdegib + LDAC arm versus 2.6% in the LDAC arm (P = 0.015). METHODS: This post hoc analysis determines whether the clinical benefits of glasdegib are restricted to patients who achieve CR, or if they extend to those who do not achieve CR. RESULTS: In patients who did not achieve CR, the addition of glasdegib to LDAC improved overall survival (OS) versus LDAC alone (hazard ratio = 0.63 [95% confidence interval, 0.41-0.98]; P = 0.0182; median OS, 5.0 vs 4.1 months). Additionally, more patients receiving glasdegib + LDAC achieved durable recovery of absolute neutrophil count (≥ 1000/μl, 45.6% vs 35.5%), hemoglobin (≥ 9 g/dl, 54.4% vs 38.7%), and platelets (≥ 100,000/μl, 29.8% vs 9.7%). Transfusion independence was achieved by 15.0% and 2.9% of patients receiving glasdegib + LDAC and LDAC alone, respectively. CONCLUSIONS: Collectively, these data suggest that there are clinical benefits with glasdegib in the absence of CR. TRIAL REGISTRATION: ClinicalTrials.gov NCT01546038 (March 7, 2012).