On March 6, 2024, inotuzumab ozogamicin (Besponsa) 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
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%, 95% confidence interval [CI] = 28.1%–55.9%); median duration of complete remission was 8.2 months (95% CI = 2.6 months to not evaluable). 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.
How It Is Used
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
OF NOTE
Inotuzumab ozogamicin has a boxed warning for hepatic toxicity and increased risk of post-HSCT nonrelapse mortality. It also has warnings/precautions for myelosuppression, infusion-related reactions, QT interval prolongation, and embryofetal toxicity.
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. Premedication with a corticosteroid, an antipyretic, and an antihistamine is recommended prior to dosing.
Safety Profile
Among the 53 patients in ITCC-059, the most common adverse events of any grade were pyrexia (49%), anemia (45%), vomiting (45%), infection (43%), hemorrhage (42%), nausea (32%), febrile neutropenia (28%), abdominal pain (25%), and headache (21%). 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 (ALT), and gamma-glutamyl transferase were observed in 21%, 21%, and 27% of patients.
KEY POINTS
- Inotuzumab ozogamicin was approved for pediatric patients aged 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia.
- For the first cycle, the recommended inotuzumab ozogamicin dose is 1.8 mg/m2 per cycle, given as three divided doses on days 1, 8, and 15.
Serious adverse events occurred in 62% of patients, most commonly infection (21%), febrile neutropenia (17%), hepatic veno-occlusive disease (15%), pyrexia (6%), and hemorrhage (4%). Adverse events led to discontinuation of treatment in 21%, most commonly (≥ 2 patients) increased ALT and decreased platelets. Fatal adverse events occurred in 8% of patients, including multiorgan failure, lung infection, sepsis, and encephalopathy.
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.
