Inotuzumab Ozogamicin Demonstrates High Response Rates in Pediatric Patients With Very High-Risk First Relapse B-Cell Acute Lymphoblastic Leukemia

Clinical Summary:

• Design/Population: The phase 1/2 ITCC-059 study evaluated single-agent inotuzumab ozogamicin in pediatric patients with CD22-positive very high-risk first relapse B-cell acute lymphoblastic leukemia.
• Key Outcomes: Among the first 31 evaluable patients, inotuzumab ozogamicin achieved an overall response rate of 71%. The safety profile was characterized primarily by hematologic toxicities and infections, with no treatment-related deaths reported.
• Clinical Relevance: These findings support inotuzumab ozogamicin as a promising reinduction strategy for pediatric patients with very high-risk first relapse B-cell acute lymphoblastic leukemia.

Results from cohort 3 of the phase 1/2 ITCC-059 trial demonstrated that inotuzumab ozogamicin produced high response rates with a manageable safety profile in pediatric patients with very high-risk first relapse of B-cell acute lymphoblastic leukemia, supporting its use as a reintroduction strategy in this difficult-to-treat population. 

“Children with very high-risk first relapse of B-cell acute lymphoblastic leukemia have very poor outcomes with conventional chemotherapy,” stated Nicolò Peccatori, MD, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands, and coauthors. “Inotuzumab ozogamicin has shown high antitumoral activity in second or higher relapsed or refractory B-cell acute lymphoblastic leukemia.”

In this single-arm trial, 37 patients older than 1 year and younger than 18 years with CD22-positive very high-risk first relapse B-cell acute lymphoblastic leukemia received 1.8 mg/m² of inotuzumab ozogamicin intravenously during cycle 1 (0.8 mg/m² on day 1 and 0.5 mg/m² on days 8 and 15), followed by 1.5 mg/m² per cycle (0.5 mg/m² on days 1, 8, and 15) for responding patients, for a maximum of 6 treatment cycles. 

The primary end point was overall response rate (ORR), defined as complete remission, complete remission with insufficient platelet recovery, or complete remission without recovery of blood counts.  A key secondary end point was safety. 

Among the first 31 enrolled patients included in the primary efficacy analysis, 22 achieved an objective response, corresponding to an ORR of 71%. 

Grade 3/4 laboratory abnormalities occurred in all treated patients. The most common were neutropenia (95%) and thrombocytopenia (84%). The most common non-hematologic grade 3/4 adverse events were febrile neutropenia (30%), infections (22%), aspartate aminotransferase elevation (32%), and alanine aminotransferase elevation (27%). 

Serious adverse events occurred in 46% of patients. No treatment-related deaths were reported. Among the 23 patients who subsequently underwent hematopoietic stem cell transplantation, sinusoidal obstruction syndrome developed in 4 patients (17%), with all cases resolving following treatment with defibrotide.

“Inotuzumab ozogamicin showed high activity as reinduction treatment in pediatric very high risk first B-cell acute lymphoblastic leukemia relapse and a favorable toxicity profile with no treatment-related deaths,” concluded Dr Peccatori et al. 

Source:

Peccatori N, Locatelli F, Ammerlaan ACJ, et al. Inotuzumab ozogamicin in pediatric very high risk first B-cell acute lymphoblastic leukaemia relapse (ITCC-059): A multicentre, single-arm, phase 2 trial. Lancet Haematol. Published online: June 15, 2026. doi: 10.1016/S2352-3026(26)00104-3