AML-140: Effect of Early Blood Counts on Response and Overall Survival Following Glasdegib Plus LDAC in Newly Diagnosed AML: BRIGHT AML 1003 Post Hoc Analysis

Abstract

Context The BRIGHT AML 1003 randomized phase 2 study ( NCT01546038 ) compared glasdegib (GLAS) plus LDAC vs LDAC-alone in patients with newly diagnosed AML or high-risk MDS who were ineligible for intensive chemotherapy. Addition of GLAS to LDAC approximately doubled overall survival (OS) without significant worsening of myelosuppression-related complications ostensibly by targeting leukemic stem cells dependent on the hedgehog pathway, which is not involved in normal adult hematopoiesis. Objective Evaluate potential association of outcomes with early blood count recovery. Design Patients were randomized 2:1 to open-label GLAS+LDAC or LDAC-alone (first patient visit Jan-2014), and continued treatment to a maximum of 4 years (final data cutoff April 2019). Setting Multicenter (European and North American centers). Patients This analysis included patients with AML (78 GLAS+LDAC; 38 LDAC-alone). Interventions Glasdegib 100 mg QD; LDAC 20 mg BID × 10 days q28 days. Main outcome measures The study primary endpoint was OS (previously published: Cortes et al., 2019, HR 0.51; p=0.0004). This post hoc analysis compared outcomes with GLAS+LDAC vs LDAC-alone in subgroups according to cell counts at cycle 2 day 1 (C2D1), using thresholds for absolute neutrophil count (ANC) ≥ 1000 or 500/μL, hemoglobin ≥ 10 or 9 g/dL, and platelets ≥ 100,000 or 50,000/μL. Results Among all patients regardless of baseline ANC, hemoglobin or platelets, achievement of thresholds at C2D1 was associated with improved OS with GLAS+LDAC (all comparisons p Conclusions In these patients, improved OS was associated with various blood count thresholds after 1 cycle of GLAS+LDAC vs LDAC-alone. In patients with baseline measurements below threshold, recovery of hemoglobin and platelet thresholds was associated with improved OS. Platelet recovery correlated with response in the GLAS+LDAC group. These exploratory results are consistent with the hematopoiesis-sparing mechanism of GLAS, and merit further evaluation. Study sponsor Pfizer.