On March 6, the U.S. Food and Drug Administration (FDA) approved the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin (Besponsa) for pediatric patients aged 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL).
Study WI203581
Efficacy was evaluated in the multicenter, single-arm, open-label WI203581 study (ClinicalTrials.gov identifier NCT02981628) in 53 pediatric patients aged 1 year and older with relapsed or refractory CD22-positive B-cell precursor ALL. Two dose levels were evaluated: an initial dose of 1.4 mg/m2/cycle in 12 patients, and 1.8 mg/m2/cycle in 41 patients. Premedications included methylprednisolone at 1 mg/kg (maximum of 50 mg), an antipyretic, and an antihistamine. Patients received a median of two cycles of therapy (range = 1–4 cycles).
The main efficacy outcome measures were complete remission, duration of complete remission, and the proportion of patients with undetectable measurable residual disease complete remission. Complete remission was defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemia blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 109 and absolute neutrophil count ≥ 1 × 109/L), and resolution of any extramedullary disease. MRD was defined by leukemic cells comprising < 1 × 10-4 (< 0.01%) of bone marrow nucleated cells by flow cytometry or by polymerase chain reaction (PCR).
In all patients, 22 of 53 (42%, 95% confidence interval [CI] = 28.1%–55.9%) achieved complete remission, and the median duration of complete remission was 8.2 months (95% CI = 2.6 months to not evaluable). The undetectable MRD rate in patients with complete remission was 21 of 22 (95.5%, 95% CI = 77.2–99.9) based on flow cytometry, and 19 of 22 (86.4%, 95% CI = 65.1–97.1) based on real-time quantitative reverse transcriptase PCR.
The most common adverse reactions (≥ 20%), including laboratory abnormalities, in patients receiving inotuzumab ozogamicin were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
For the first cycle, the recommended inotuzumab ozogamicin dose is 1.8 mg/m2 per cycle, administered 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 the patient achieves a complete remission or complete remission with incomplete hematologic recovery, and/or to allow recovery from toxicity. See the prescribing information for the recommended dosage after the first cycle.
This application was granted Priority Review and Orphan Drug designation.
