On March 6, 2024, the anti-CD22 monoclonal antibody inotuzumab ozogamicin (Besponsa), which is bound to a toxic natural calicheamicin, was approved for pediatric patients aged 1 year or older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia.¹

Supporting Efficacy Data and How It Is Used

Approval was based on findings in the ITCC-059 trial (ClinicalTrials.gov identifier NCT02981628), in which 53 patients (median age = 9 years, range = 1–17 years) received initial intravenous doses of 1.4 mg/m²/cycle (n = 12) or 1.8 mg/m²/cycle (n = 41). Complete remission was achieved in 22 patients (42%); median duration of complete remission was 8.2 months. Among patients with complete remission, measurable residual disease status was negative for 21 (95.5%) on flow cytometry and for 19 (86.4%) on polymerase chain reaction assay.

For the first cycle, the recommended inotuzumab ozogamicin dose is 1.8 mg/m² per cycle, given as three divided doses on day 1 (0.8 mg/m²), day 8 (0.5 mg/m²), and day 15 (0.5 mg/m²). Cycle 1 is 3 weeks in duration but may be extended to 4 weeks if patients achieve complete remission or complete remission with incomplete hematologic recovery or to allow recovery from toxicity. Product labeling provides instructions on dosage for subsequent cycles. Recommended duration of treatment is two cycles in patients proceeding to hematopoietic stem cell transplantation (HSCT) and up to six cycles in those not proceeding to HSCT.

Safety Profile

Among the 53 patients in ITCC-059, the most common grade ≥ 3 adverse events included anemia (38%), febrile neutropenia (28%), infection (23%), hepatic veno-occlusive disease (13%), and tumor-lysis syndrome (11%). The most common grade 3 or 4 laboratory abnormalities were hematologic, ranging from 42% (decreased hemoglobin) to 96% (decreased neutrophils); grade ≥ 3 increased aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase were observed in 21%, 21%, and 27% of patients. respectively.

Serious adverse events occurred in 62% of patients. Adverse events led to discontinuation of treatment in 21%. Fatal adverse events occurred in 8% of patients.

Inotuzumab ozogamicin has a boxed warning for hepatic toxicity, including hepatic veno-occlusive disease, and increased risk of post-HSCT nonrelapse mortality. It also has warnings/precautions for myelosuppression, infusion-related reactions, QT interval prolongation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving inotuzumab ozogamicin. 

REFERENCE

1. Besponsa (inotuzumab ozogamicin) for injection, for intravenous use, prescribing information, Pfizer, March 2024. Available at besponsa.pfizerpro.com. Accessed March 18, 2024.