Bosutinib Approved for Pediatric Patients With Chronic Myelogenous Leukemia

Chronic myelogenous leukemia in accelerated phase.

The FDA has approved bosutinib (Bosulif®, Pfizer) for treatment of pediatric patients with newly diagnosed or resistant/intolerant to prior therapy chronic phase (CP) Philadelphia chromosome (Ph)–positive chronic myelogenous leukemia (CML). In addition, the FDA has approved a new capsule dosage available as 50 mg and 100 mg.  

Why it matters: “Bosutinib is a tyrosine kinase inhibitor (TKI), approved for adults with Ph-positive CML,” wrote Edoardo Pennesi, a Doctoral Researcher at Princes Maxima Center for Pediatric Oncology, and colleagues, in their preliminary results of the BCHILD trial (NCT04258943), on which approval was based. “Compared to the TKIs already approved in pediatrics, bosutinib has a different tolerability profile, and preclinical data suggest that longitudinal growth is potentially less impaired.”

What they studied: Safety, tolerability, and efficacy were studied in the phase 1/2, multicenter, single-arm, open-label trial in which 49 pediatric patients with newly diagnosed or resistant/intolerant to prior therapy CP Ph-positive CML were enrolled. Twenty-eight patients received 300 mg/m2 to 400 mg/m2 of bosutinib orally, once daily, and 21 patients received 300 mg/m2 orally, once daily.

The primary end points measured were major cytogenetic response (MCyR), complete cytogenetic response (CCyR), and major molecular response (MMR).

What they found: At a median follow-up of 14.2 months for pediatric patients with newly diagnosed CP Ph-positive CML receiving bosutinib, the MCyR was seen at 76.2%, the CCyR was seen at 71.4%, and the MMR was seen at 28.6%.

At a median follow-up of 23.2 months for pediatric patients with resistant/intolerant CP Ph-positive CML receiving bosutinib, MCyR was seen at 82.1%, CCyR was seen at 78.6%, and MMR was seen at 50%. Of the 14 patients who achieved MMR, two lost MMR after 13.6 and 24.7 months on treatment, respectively.

Adverse events: The most common adverse events experienced by ≥20% of pediatric patients were diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥45% of pediatric patients were increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.

Conclusion: “Bosutinib was well tolerated, despite common grade 1-2 gastrointestinal adverse events,” concluded Dr. Pennesi and colleagues. “The preliminary efficacy seems comparable to published data from other second-generation TKIs in children and to newly diagnosed adult patients treated with bosutinib.”

Instructions: The recommended dosage of bosutinib for pediatric patients with newly diagnosed CP Ph-positive CML is 300 mg/m2 orally, once daily with food. The recommended dosage for pediatric patients with resistant/intolerant CP Ph-positive CML is 400 mg/m2 orally, once daily with food. For patients who are unable to swallow capsules, the content of the capsule can be mixed with applesauce or yogurt.

For More Information

Pennesi E, Brivio E, Willemse ME, et al (2023). Preliminary results from the first-in-child phase II trial (ITCC-054/COG-AAML1921) of bosutinib in pediatric patients with newly diagnosed (ND) chronic myeloid leukemia (CML). J Clin Oncol, 41(suppl_16). Abstract 10017. DOI:10.1200/JCO.2023.41.16_suppl.10017

Clinicaltrials.gov (2023). Bosutinib in pediatric patients with newly diagnosed chronic phase or resistant/intolerant Ph + chronic myeloid leukemia. NLM identifier: NCT04258943.

Bosulif® (bosutinib) prescribing information (2023). Pfizer. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/203341s025lbl.pdf

US Food and Drug Administration (2023). FDA approves bosutinib for pediatric patients with chronic myelogenous leukemia. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bosutinib-pediatric-patients-chronic-myelogenous-leukemia

Image credit: El Falaf. Licensed under CC BY-SA 4.0


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