In this post-hoc analysis, data from the BRIGHT AML 1003 study were used to evaluate the potential association of early blood counts with overall survival (OS) or leukemia response among patients receiving glasdegib (GLAS) plus low-dose cytarabine (LDAC) or LDAC alone. Patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy were randomized to GLAS + LDAC (N = 78) or LDAC alone (N = 38). GLAS was given once daily and LDAC was given on days 1 to 10 of a 28-day cycle. Peripheral blood counts were measured at cycle 2, day 1 (C2D1), approximately 1 month prior to the first bone marrow assessments. OS was compared between GLAS + LDAC and LDAC in subgroups meeting thresholds of absolute neutrophil count (ANC; ≥1000 or 500/µL), hemoglobin (Hb; ≥10 or 9 g/dL), or platelets (≥100,000 or 50,000/µL). Patients were included in this analysis regardless of transfusion status. The data cutoff for this analysis was April 2019.
Among all patients, attaining the aforementioned ANC, Hb, and platelet thresholds at C2D1 was associated with improved median OS (mOS) to a greater extent for patients receiving GLAS + LDAC versus LDAC alone, as follows: ANC 0.5 x 103: 9.0 months versus 4.9 months (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.21-0.76; P = .002), ANC 103: 7.4 months versus 3.8 months (HR, 0.36; 95% CI, 0.16-0.81; P = .005), Hb ≥9: 12.4 months versus 4.9 months (HR, 0.35; 95% CI, 0.17-0.72; P = .002), Hb ≥10: 8.7 months versus 3.0 months (HR, 0.33; 95% CI, 0.12-0.87; P = .009), platelets ≥0.5 x 105: 14.9 months versus 4.7 months (HR, 0.22; 95% CI, 0.09-0.50; P <.001), and platelets ≥105: 18.5 months versus 4.3 months (HR, 0.17; 95% CI, 0.06-0.51; P <.001), respectively. Similar OS benefits for GLAS + LDAC compared with LDAC alone were observed among patients who did not meet ANC, Hb, or platelet thresholds at C2D1. Patients with baseline anemia or thrombocytopenia also had improved OS associated with C2D1 recovery of Hb or platelets, with mOS for GLAS + LDAC versus LDAC as follows: Hb ≥9: 9.1 months versus 2.9 months (HR, 0.16; 95% CI, 0.04-0.62; P = .001) or Hb ≥10: 9.1 months versus 2.9 months (HR, 0.27; 95% CI, 0.07-0.95; P = .015); and platelets ≥0.5 x 105: 19.1 months versus 6.4 months (HR, 0.19; 95% CI, 0.04-0.82; P = .007) or platelets ≥105: 19.6 months versus 5.1 months (HR, 0.13; 95% CI, 0.03-0.53; P <.001), respectively. Any degree of response (complete response [CR]/CR with incomplete hematologic recovery/partial response) to GLAS + LDAC correlated with achieving platelet thresholds at C2D1, including recovery in patients with baseline thrombocytopenia. Of the 13 patients in the GLAS + LDAC arm with baseline platelets <0.5 x 105 who achieved C2D1 platelets ≥105, 11 (84.6%) were responders compared with 2 (15.4%) who were nonresponders (P <.0001).
In conclusion, improved OS was associated with attaining various blood count thresholds after 1 cycle of GLAS + LDAC versus LDAC alone in patients with newly diagnosed AML who were not eligible for intensive chemotherapy. In addition, recovery of Hb and platelet thresholds was associated with improved OS among patients with baseline measurements below threshold. Finally, platelet recovery was correlated with response in the GLAS + LDAC group.
Wang ES, Heuser M, Sekeres MA, et al. Effect of Early Blood Counts on Response and Overall Survival Following Glasdegib plus LDAC in Newly Diagnosed AML: Bright AML 1003 Post Hoc Analysis. Presented at: 25th European Hematology Association Congress Virtual; June 11-21, 2020. Abstract EP633.