Bosutinib Approved by FDA for Pediatric Patients With Chronic Myelogenous Leukemia

The FDA has approved bosutinib (Bosulif) to treat pediatric patients aged 1 year or older with Philadelphia chromosome (Ph)–positive chronic-phase chronic myelogenous leukemia (CP-CML) that is newly diagnosed, resistant, or intolerant to previous therapy. The FDA also approved a new capsule dose form at 50 mg and 100 mg.¹

The approval was based on findings from the multicenter, nonrandomized, open-label, phase 1/2 BCHILD trial (NCT04258943). The trial enrolled pediatric patients between 1 and 17 years of age who had a cytogenetic and molecular diagnosis of Ph-positive CML, either at the time of initial diagnosis or during screening.²

For enrollment criteria, newly diagnosed patients were required to have Ph-positive CP-CML within 6 months of the initial diagnosis without prior tyrosine kinase inhibitor (TKI) treatment for CML, other than for hydroxyurea and/or anagrelide. Patients with resistant/intolerant CP-CML were required to have resistance as defined by 2013 European Leukemia Net guidelines or intolerance to at least 1 prior TKI.

Other enrollment criteria required patients ≤16 years of age to have a Lansky performance status of at least 50% or required patients >16 years of age to have a Karnofsky performance status of at least 50%. Patients were also required to have adequate bone marrow function, neutrophil count, and renal function.

Exclusion criteria included primary Ph-positive acute lymphoblastic leukemia, extramedullary disease only, or documented BCR-ABL1 T315I or V299L mutations. In phase 1 of the trial, patients with resistant/intolerant Ph-positive CP-CML were administered 400 mg/m² of oral bosutinib once daily.

After establishing the recommended phase 2 dose, patients with resistant or intolerant disease were treated at the RP2D in phase 2. Those with newly diagnosed disease were only enrolled during phase 2 of the trial and were administered 300 mg/m² of oral bosutinib once daily.

The study showed that at a median follow-up of 14.2 months (range, 1.1-26.3), pediatric patients with newly diagnosed Ph-positive CP-CML (n = 21) had a major cytogenetic response (MCyR) rate of 76.2% (95% CI, 52.8%-91.8%) and a complete cytogenetic response (CCyR) rate of 71.4% (95% CI, 47.8%-88.7%). Further, major molecular response (MMR) was 28.6% (95% CI, 11.3%-52.3%).

Among pediatric patients with resistant/intolerant Ph-positive CP-CML (n = 28), the trial found that at a median follow-up of 23.2 months (range, 1-61.5), the rate of MCyR was 82.1% (95% CI, 63.1%-93.9%), rates of CCyR were 78.6% (95% CI, 59%-91.7%), and MMR was 50% (95% CI, 30.6%-69.4%). Two patients among 14 who achieved MMR lost it after 13.6 and 24.7 months of treatment, respectively.

According to the FDA, the recommended dose of bosutinib for pediatric patients with newly diagnosed Ph-positive CP-CML is 300 mg/m² orally once daily with food, whereas the recommended dose for pediatric patients with resistant/intolerant Ph-positive CP-CML is 400 mg/m² orally once daily with food.

The most common adverse effects occurring in at least 20% of pediatric patients consisted of 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 at least 45% of pediatric patients included increased creatinine, increased alanine aminotransferase, increased aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.

References

1. FDA approves bosutinib for pediatric patients with chronic myelogenous leukemia. News release. FDA. September 26, 2023. Accessed September 27, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bosutinib-pediatric-patients-chronic-myelogenous-leukemia

2. Bosutinib in pediatric patients with newly diagnosed chronic phase or resistant/intolerant Ph+ chronic myeloid leukemia. ClinicalTrials.gov. Updated August 31, 2023. Accessed September 27, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04258943