Inotuzumab ozogamicin dose optimization in R/R ALL

An evaluation of dose-optimization strategies for single-agent inotuzumab ozogamicin (InO) in adults with relapsed/refractory (R/R) CD22+ B-cell precursor acute lymphoblastic leukemia (ALL) were published in Leukemia & Lymphoma by DeAngelo et al. The review follows a post-marketing requirement issued by the FDA, reflecting concerns that the proposed dose of 1.8 mg/m²/cycle may not optimally balance the safety and efficacy of InO monotherapy.

Key data: Based on pooled data from the phase I/II B1931010 (NCT01363297) and phase III INO-VATE (NCT01564784) trials, the starting dose of 1.8 mg/m²/cycle had a greater clinical utility index (CUI) compared with lower doses in patients with median exposure, regardless of whether they proceeded to post-treatment hematopoietic stem cell transplantation (HSCT). In the phase IV post-marketing requirement study (NCT03677596), which included patients at higher risk of veno-occlusive disease (VOD) / sinusoidal obstruction syndrome (SOS), the starting dose of 1.8 mg/m²/cycle had a greater CUI compared with 1.2 mg/m²/cycle in a R/R ALL patient with median exposure at the respective dose. The complete remission (CR) / CR with incomplete hematologic recoery recovery (CRi) rates at 1.2 mg/m²/cycle and 1.8 mg/m²/cycle were 71.9% and 68.4%, respectively; among responders, MRD-negativity rates were 71.7% and 69.2%, respectively. VOD rates post-HSCT at 1.2 mg/m²/cycle and 1.8 mg/m²/cycle were 25.8% and 16.7%, respectively.

Key learning: This analysis supports the current FDA-approved dose for InO monotherapy of 1.8 mg/m²/cycle as providing a favorable balance of safety and efficacy, although dosing may be individualized according to treatment setting and transplant-related VOD/SOS risk.