Dose-dependent outcomes with inotuzumab ozogamicin in B-ALL

Inotuzumab ozogamicin (InO) is approved for the treatment of relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL).¹ Based on findings from the phase III INO-VATE trial, limiting InO to two cycles before hematopoietic stem cell transplantation is recommended to mitigate the risk of hepatic sinusoidal obstruction syndrome.¹

During the European Hematology Association (EHA) 2025 Congress, Elias Jabbour presented results from a pooled analysis of three clinical trials (NCT01363297, NCT01564784, NCT03677596), assessing InO outcomes in adults with R/R B-ALL (N = 338).¹ Patients were grouped by cumulative InO dose, and the analysis focused on those who responded after one cycle of treatment (≤3.3 mg/m², n = 62; >3.3 mg/m², n = 109).¹

Key learnings 

12-month PFS (44.0% vs 21.2%) and OS (51.6% vs 37.9%) rates were higher in the ≤3.3 mg/m² cohort compared with the >3.3 mg/m² cohort. Median OS was also improved in the lower dose cohort (12.2 months vs 9.2 months).

More patients proceeded to HSCT in the ≤3.3 mg/m² cohort compared with the >3.3 mg/m² cohort (74% vs 46%), and post-HSCT mortality and NRM were lower with ≤3.3 mg/m² than with >3.3 mg/m² InO (39% vs 62%; 28% vs 44%, respectively).

Overall safety profiles were similar between doses. Any-grade post-HSCT SOS rates were the same in both cohorts (24%), while Grade 3–4 post-HSCT SOS rates were also similar between cohorts. 

Improved survival outcomes with the ≤3.3 mg/m² vs >3.3 mg/m² dose of InO may be attributed to more patients proceeding to HSCT in the lower dose cohort. Further investigation of strategies to reduce SOS risk and transplant-related mortality and optimal InO dose is warranted.