Single-center phase 1 dose-escalation study of dose-adjusted EPOCH plus inotuzumab ozogamicin in adults with R/R B-ALL

New approaches are needed for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (R/R B-ALL). A phase 1 dose-escalation trial at the University of Washington (Seattle) evaluated the combination of inotuzumab ozogamicin (InO) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) for R/R B-ALL in adult patients. The 24 patients received DA-EPOCH on days 1 to 5, while InO was given on day 8 and 15 of each 28-day cycle. The dose level of InO (0.6 mg/m²) was the maximum tolerated dose. Significant severe hepatic toxic effects were rare, and there was only 1 case of sinusoidal obstructive syndrome. The overall response rate was 83%, median overall survival was 17.0 months, median duration of response was 15.0 months, and median event-free survival was 9.6 months. The authors conclude that the combination of DA-EPOCH and InO is a safe, well-tolerated, and clinically active chemoimmunotherapy regimen for R/R B-ALL in adult patients.