Venetoclax Plus Inotuzumab Shows Activity in Phase 1 Relapsed ALL/LBL Trial

Responses to inotuzumab ozogamicin in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are often short-lived. A phase 1 trial evaluated its combination with venetoclax in 23 adults with CD22-positive disease: 15 with ALL and eight with LBL. Venetoclax doses of 200 and 400 mg/day were tested alongside standard-dose inotuzumab, followed by expansion at 400 mg/day.

The recommended venetoclax dose was 400 mg/day for 21 days per cycle. No dose-limiting toxicities or early deaths occurred. The most frequent grade ≥3 adverse events were thrombocytopenia (43.5%) and neutropenia (39.1%); four patients (17.4%) developed sinusoidal obstructive syndrome. Among 22 evaluable patients, 21 (95.5%) achieved complete remission, including 19 after one cycle. Measurable residual disease cleared in 16 of 18 patients assessed by flow cytometry and 14 of 19 assessed by next-generation sequencing.

Fourteen patients proceeded to hematopoietic stem cell transplantation. At a median follow-up of 25.3 months, estimated two-year disease-free and overall survival were both 48% (95% CI, 24–72%). Median disease-free survival was 22.1 months; median overall survival was not reached. These findings support further evaluation, but the small phase 1 cohort, absence of a reported comparator, and subsequent transplantation limit conclusions about the combination’s survival benefit. This update is based on the abstract; full text was unavailable.