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Inotuzumab Ozogamicin Approved for Pediatric Patients with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia.

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."

Tristan Knight, MD, FRCPC.

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/m2 per 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. 

Conclusion: "In children with relapsed B-ALL, one of the single greatest predictors of subsequent survival is the ability to achieve an MRD-negative status," added Dr Knight. "Inotuzumab ozogamicin is a critical addition to the armamentarium of pediatric oncologists in the battle to achieve this goal. Specifically, prior to taking a child to HSCT, remission induction with inotuzumab is a useful option by which MRD negativity may be achieved—although attention must be paid to the heightened risk of SOS associated with its use."

Instructions: The recommended dosage for the first cycle is 1.8 mg/m2 of inotuzumab ozogamicin 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 typically has a three-week duration, but it may be extended to four weeks if the patient achieves a complete remission or a complete remission with incomplete hematologic recovery, and/or to allow recovery from toxicity. Please refer to the prescribing information for recommended dosing following the first cycle.

For More Information

O'Brien MM, Ji L, Shah NN, et al (2022). Phase II trial of inotuzumab ozogamicin in children and adolescents with relapsed or refractory b-cell acute lymphoblastic leukemia: children's oncology group protocol AALL1621. J Clin Oncol, 40(9):956-967. DOI:10.1200/JCO.21.01693 (2024). Inotuzumab ozogamicin in treating younger patients with b-lymphoblastic lymphoma or relapsed or refractory CD22 positive B acute lymphoblastic leukemia. NLM identifier: NCT02981628.

Besponsa™ (inotuzumab ozogamicin) prescribing information (2024). Pfizer. Available at:

US Food and Drug Administration (2024). FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia. Available at:

Image credit: Animalculist. Licensed under CC BY-SA 4.0

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