Venetoclax + inotuzumab ozogamicin in R/R ALL: Phase I results

Results from a phase I trial (NCT05016947), investigating venetoclax (Ven), a B-cell lymphoma 2 (BCL-2) inhibitor, plus inotuzumab ozogamicin (InO), an anti-CD22 antibody–drug conjugate, in 23 adult patients with relapsed/refractory (R/R) CD22+ acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL), were presented by Marlise Luskin at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US. The primary objective was to determine the maximum tolerated dose (MTD) of Ven + InO. Secondary objectives were to determine the preliminary efficacy of the combination. Patients were assigned to dose level (DL) 1 (n = 3), DL2 (n = 6), or dose expansion (n = 14).

Key data: No cases of early mortality were reported. The most common hematologic Grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (43.5%), leukopenia (39.1%), and neutropenia (39.1%). Febrile neutropenia was reported in 8.7% of patients, while four cases of sinusoidal obstructive syndrome (SOS) were reported. The complete remission (CR) rate was 95.5% (21/22), with 100% (15/15) of ALL patients and 85.7% (6/7) of LBL patients achieving CR. Measurable residual disease (MRD)-negativity was achieved by flow cytometry (<0.01%) and next-generation sequencing (NGS; <0.0001%) in 88.9% (16/18) and 73.7% (14/19) of patients, respectively. Median disease-free survival (DFS) and overall survival (OS) were 36.1 months and not reached (NR), respectively.

Key learning: Adding Ven to InO in patients with R/R CD22+ ALL or LBL demonstrated a durable rate of MRD-negativity, with a manageable safety profile, supporting the continued evaluation of BCL-2 inhibitors + InO vs single-agent InO in this patient population.