Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia.

In the phase 3 TOWER study, blinatumomab demonstrated an overall survival benefit over standard-of-care chemotherapy (SOC) in adults with relapsed or refractory (r/r) Philadelphia chromosome-negative (Ph) B-precursor acute lymphoblastic leukemia (ALL). Nearly all patients in both treatment arms experienced an adverse event (AE), and the incidence rate of serious AEs was higher for blinatumomab. However, as treatment exposure differed between the 2 arms, we conducted an exploratory safety analysis comparing exposure-adjusted event rates (EAERs) of blinatumomab vs SOC. Analyses were conducted for all patients who received therapy (safety population). Patients received a median (range) of 2 cycles (1-9) of blinatumomab (N = 267) vs 1 cycle (1-4) of SOC (N = 109). Grade ≥3 AE rates were generally higher in cycle 1 of blinatumomab than in cycle 2 (76% vs 37%). After adjusting for time on treatment, EAERs of grade ≥3 were significantly lower for blinatumomab vs SOC overall (10.73 vs 45.27 events per patient-year; < .001) and for events of clinical interest, including infections (1.63 vs 6.49 events per patient-year; < .001), cytopenias (3.64 vs 20.07 events per patient-year; < .001), and neurologic events (0.38 vs 0.95 events per patient-year; = .008). The EAER of grade ≥3 cytokine-release syndrome was higher for blinatumomab than for SOC (0.16 vs 0 events per patient-year; = .038). These data further support the role of blinatumomab as an efficacious and well-tolerated treatment option for patients with r/r Ph ALL. This trial was registered at www.clinicaltrials.gov as #NCT02013167.