FDA Approves Inotuzumab for Pediatric Patients with ALL

White blood cells in leukemia, AI Generative: © Катерина Євтехова - stock.adobe.com

• Inotuzumab ozogamicin (Besponsa), a novel monoclonal antibody, has been approved by the FDA for the treatment of pediatric patients 1 year or older with relapsed/refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL).
• The approval is supported by a phase 2 study (NCT02981628).
• Inotuzumab was granted priority review and orphan drug designation, highlighting its need in this intent-to-treat (ITT) population.

The FDA has approved inotuzumab for the treatment of patients 1 year or older with relapsed or refractory CD22-positive B-cell precursor ALL.¹

The approval is supported by findings from a phase 2 study evaluating 53 pediatric patients. Twenty-two patients achieved a complete response (CR; 42%; 95% CI, 28.1%-55.9%). The median duration of CR was 8.2 months (95% CI, 2.6-not evaluable). In patients who achieved a CR, the minimal residual disease (MRD) negativity rate was 95.5% (n = 21; 95% CI, 77.2%-99.9%) based on flow cytometry.

Regarding safety, the most common adverse events were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.

In the first cycle, inotuzumab is recommended to be dosed at 1.8 mg/m2 split between days 1, 8, and 15. The first cycle is 3 weeks long but can be extended to 4 weeks if the patient achieves a complete remission or to allow recovery from any presenting toxicities.

In 2017, the FDA approved inotuzumab for adult patients with relapsed/refractory B-cell precursor ALL. In a long-term follow-up of patients in this ITT population, the 2-year progression-free survival rate was 58.2% (95% CI, 46.7%-68.2%), and the 5-year rate was 44.0% (95% CI, 31.2%-54.3%).²

The phase 2 trial of inotuzumab is still active but no longer recruiting.³ It has an anticipated completion date of December 2024. The study’s primary end point is morphologic CR rate, and secondary end points include incidence of dose-limiting toxicities, level of MRD, event-free survival, overall survival, duration of CR, and pharmacokinetics.

REFERENCES:

1. FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia. U.S. Food and Drug Administration. March 6, 2024. Accessed March 6, 2024. https://tinyurl.com/45fn6vda

2. Jabbour E, Short NJ, Senapati J, et al. Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukemia: long-term results of an open-label phase 2 trial. Lancet Haematol. 2023;10(6):e433-e444. doi:10.1016/S2352-3026(23)00073-X

3. Inotuzumab ozogamicin in treating younger patients with B-lymphoblastic lymphoma or relapsed or refractory CD22 positive B acute lymphoblastic leukemia. ClinicalTrials.gov. Updated February 28, 2024. Accessed March 6, 2024. https://clinicaltrials.gov/study/NCT02981628