Inotuzumab Ozogamicin Shows 71% Response Rate in Children with Very High-Risk First B-Cell ALL Relapse

A phase 2 study published in The Lancet Haematology reported substantial activity for single-agent inotuzumab ozogamicin in children with very high-risk first relapse of B-cell acute lymphoblastic leukaemia (B-ALL). Among the first 31 patients in the primary efficacy population, 22 responded, producing an overall response rate (ORR) of 71% (80% CI 58–82).

ITCC-059 Evaluated Inotuzumab in Very High-Risk First Relapse

The findings came from cohort 3 of ITCC-059 (NCT02981628), a multicentre, international, single-arm phase 1–2 trial. The cohort enrolled children older than 1 year and younger than 18 years with CD22-positive very high-risk first B-ALL relapse at 20 hospitals across 12 countries. Very high-risk relapse included isolated bone marrow or combined relapse within 18 months of diagnosis, or relapse with high-risk features such as KMT2A::AFF1, TCF3::PBX1, TCF3::HLF, hypodiploidy or TP53 mutation/deletion.

Between April 26, 2021, and February 11, 2025, 45 patients were screened; eight were excluded and 37 were treated. Median age was 11 years (IQR 4–15), with 22 (59%) male and 15 (41%) female patients.

Primary Endpoint Met With 71% ORR

The primary endpoint was ORR, defined as complete remission, complete remission with insufficient platelet recovery, or complete remission without count recovery. Because of slow recruitment, the statistical design was amended to reduce the required sample size, making the first 31 enrolled patients the primary efficacy population.

Inotuzumab was administered intravenously at 1.8 mg/m² in cycle 1 (0.8 mg/m² on day 1; 0.5 mg/m² on days 8 and 15), followed by 1.5 mg/m² per cycle in responding patients, with up to six cycles permitted.

Cytopenias and Infections Among Key Safety Findings

All 37 patients had at least one grade 3–4 haematologic laboratory abnormality. Neutropenia occurred in 35 patients (95%) and thrombocytopenia in 31 (84%). Grade 3–4 febrile neutropenia occurred in 11 patients (30%), infections in eight (22%), AST elevation in 12 (32%), and ALT elevation in 10 (27%). Serious adverse events occurred in 17 patients (46%). One patient had a grade 5 lung infection, while no treatment-related deaths occurred.

Sinusoidal obstruction syndrome occurred in four of 23 transplanted patients (17%); all cases resolved after intervention with defibrotide.

Findings Add to Pediatric Treatment Evidence

The study supports inotuzumab ozogamicin as an active reinduction approach in this high-risk population, although the single-arm design and small efficacy population do not establish superiority over conventional chemotherapy or other reinduction strategies. Follow-up remains ongoing, so durability of response and longer-term outcomes remain to be determined.

The published report also notes that responses were poorer in patients with high-risk cytogenetic or molecular features, particularly TP53 alterations, highlighting an important area for further investigation. Based on data from the ITCC-059 programme, the European Medicines Agency updated the paediatric indication for inotuzumab ozogamicin on March 26, 2026.

Reference

Peccatori N, Locatelli F, Ammerlaan ACJ, et al. Inotuzumab ozogamicin in paediatric very high risk first B-cell acute lymphoblastic leukaemia relapse (ITCC-059): a multicentre, single-arm, phase 2 trial. The Lancet Haematology. 2026;13(7):e449–e459. https://doi.org/10.1016/S2352-3026(26)00104-3