Subcutaneous blinatumomab in relapsed/refractory B-ALL: Results from phase I/II dose-expansion study

Blinatumomab is a CD3/CD19 bispecific T-cell-engager molecule, approved by the U.S. Food and Drug Administration and the European Commission as an intravenous infusion for the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL).

The efficacy and safety of subcutaneous blinatumomab in patients with relapsed/refractory (R/R) B-ALL is currently under investigation in a phase I/II dose-escalation and -expansion trial (NCT04521231). Elias Jabbour presented outcomes from the dose-expansion phase of this trial during the European Hematology Association (EHA) 2025 Congress, June 12–15, 2025, Milan, IT. Patients received either 250 μg blinatumomab once daily (QD) for Week 1 of Cycle 1 and 500 μg three times a week thereafter (250 μg/500 μg; n = 36), or 500 μg blinatumomab QD and 1,000 μg three times a week thereafter (500 μg/1,000 μg; n = 52). The primary endpoint was complete remission (CR) or CR with partial hematologic recovery within two treatment cycles.

Key learnings 

Response rates were similar in both cohorts; the CR/CRh rate was 75% in the 250 μg/500 μg cohort and 79% in the 500 μg/1,000 μg cohort. Among responders, MRD negativity rates were 89% in the 250 μg/500 μg cohort and 93% in the 500 μg/1,000 μg cohort.

Median duration of response was 5 months in the 250 μg/500 μg cohort and 11 months in the 500 μg/1,000 μg cohort. The estimated 12-month OS rates were 63% and 70% in the 250 μg/500 μg and 500 μg/1,000 μg cohorts, respectively.

No fatal TRAEs were reported. Grade ≥3 CRS was observed in 17% and 23% of patients, while Grade ≥3 neurologic events were observed in 28% and 27% of patients in the 250 μg/500 μg and the 500 μg/1,000 μg cohorts, respectively; all were resolved with supportive care.

Subcutaneous blinatumomab demonstrated efficacy at 250 μg/500 μg and 500 μg/1,000 μg dose levels, with 250 μg/500 μg selected as the RP2D.