Pharmacokinetics/Pharmacodynamics (Pkpd) Of Blinatumomab In Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (R/R All).

2561 Background: Blinatumomab is a CD19-directed bispecific T-cell engager antibody construct indicated for treatment of Ph-negative r/r ALL. We evaluated blinatumomab PK/PD and explored their associations with efficacy/safety in 189 r/r ALL patients in a phase 2 study (Topp et al. Lancet Oncol 2015;16:57). Methods: Blinatumomab was given by continuous IV infusion (4 wk on/2 wk off) for ≤ 5 cycles (Cycle 1: 9 µg/d days 1–7; then 28 µg/d; thereafter: 28 µg/d). Association between exposure and measures of efficacy (complete response [CR]/CR with partial hematologic recovery [CRh] within the first 2 cycles) and safety (cytokine release syndrome [CRS]; neurologic events [NE]) was evaluated by logistic regression. Impact of covariates on exposure-response was assessed in multivariate analyses. Results: Blinatumomab PK was linear; mean (SD) serum steady state concentration (Css) at 28 µg/d was 621 (502) pg/mL in Cycle 1. IL-6, IL-10 and IFNγ were transiently elevated in u003e 50% of pts on days 1–2 of Cycle 1, much...