Inotuzumab Ozogamicin Approved for Pediatric Patients with Acute Lymphoblastic Leukemia

Tristan Knight, MD, FRCPC.

The FDA has granted approval to inotuzumab ozogamicin (Besponsa™, Pfizer) for pediatric patients one year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL).  

Why it matters: “Among adult patients with relapsed or refractory B-ALL, the use of inotuzumab ozogamicin has led to improved outcomes as compared to those treated with chemotherapy alone,” said Tristan Knight, MD, FRCPC, an Oncology Data Advisor Editorial Board Member and Clinical Assistant Professor at Seattle Children’s Hospital. “Given that only about half of children with relapsed or refractory B-ALL respond to chemotherapeutic re-induction prior to hematopoietic stem cell transplantation (HSCT), new treatment options are urgently needed in this space. The recent approval of inotuzumab ozogamicin by the FDA provides such an option.”

What they studied: Efficacy was measured in the phase 2, multicenter, single-arm, open-label trial (NCT02981628) which enrolled 53 pediatric patients one year and older with relapsed or refractory CD22-positive B-cell precursor ALL. Patients were assigned to receive one of two dose levels of inotuzumab ozogamicin for evaluation: 12 patients received an initial dose of 1.4 mg/m2 per cycle and 41 patients received an initial dose of 1.8 mg/mper cycle for up to four cycles. The median number of cycles received was two cycles of therapy (range 1 to 4 cycles). All patients received premedication consisting of 1 mg/kg of methylprednisolone—up to a 50 mg maximum—an antipyretic, and an antihistamine.

The primary end points measured were complete remission, duration of complete remission, and proportion of patients with minimal residual disease (MRD)–negative complete remission. Complete remission was defined as <5% blasts in the bone marrow and the absence of peripheral blood leukemia blasts with full recovery of peripheral blood counts (platelets ≥100 × 109/L and absolute neutrophil count ≥1 × 109/L) and resolution of any extramedullary disease. MRD was defined as leukemic cells comprising <1 × 10-4 (<0.01%) of bone marrow nucleated cells by flow cytometry or by polymerase chain reaction.

What they found: Out of the 53 patients enrolled, 22 achieved complete remission, with a median duration of complete remission at 8.2 months. Out of the 22 patients who achieved complete remission, 21 patients were MRD-negative based on flow cytometry, and 19 patients were MRD-negative based on real-time quantitative polymerase chain reaction.

Adverse events: The most common adverse events experienced in ≥20% of patients receiving inotuzumab ozogamicin, including laboratory abnormalities, were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache. The prescribing information includes a boxed warning for sinusoidal obstruction syndrome (SOS) and an increased risk of post-HSCT non-relapse mortality. 

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