FDA approves bosutinib for pediatric Ph+CP-chronic myelogenous leukemia (CML)

The FDA has approved Bosutinib (Bosutinib) for the treatment of pediatric patients 1 year and older with Philadelphia chromosome (Ph)-positive, chronic phase chronic myelogenous leukemia (CP-CML) who are newly diagnosed or who are resistant or intolerant to previous treatments. New capsule dosage forms of 50 mg and 100 mg were also approved.

The regulatory decision is supported by data from the Phase 1/2 BCHILD trial (NCT04258943), which showed that at a median follow-up of 14.2 months (range 1.1-26.3 months), newly diagnosed Ph-positive chronic In pediatric patients with myelogenous leukemia (n=21), the major cytogenetic response (MCyR) rate was 76.2% (95% CI, 52.8%-91.8%), and the overall complete cytogenetic response rate was 71.4% (95% CI, 47.8%-88.7%). In addition, the major molecular response (MMR) was 28.6% (95% CI, 11.3%-52.3%).

At a median follow-up of 23.2 months (range 1-61.5) in pediatric patients (n=28) with drug-resistant/intolerant Ph-positive chronic myelogenous leukemia, M The CyR and CCyR rates were 82.1% (95%CI, 63.1%-93.9%) and 78.6% (95%CI, 59%-91.7%) respectively. The mortality rate was 50% (95% CI, 30.6%-69.4%). Of the 14 patients who achieved MMR, 2 patients lost MMR after 13.6 and 24.7 months of treatment, respectively.

This multicenter, non-randomized, open-label BCHILD trial enrolled pediatric patients aged 1 to 17 years who had a cytogenetic and molecular diagnosis of Ph-positive CML at the time of initial CML diagnosis or at screening. 2 Newly diagnosed patients were required to have Ph-positive CP-CML within 6 months of initial diagnosis and not have received any prior TKI CML treatment, except for hydroxyurea and/or anagrelide. Patients with drug-resistant/intolerant chronic myelogenous leukemia were required to have drug resistance as defined by the 2013 European Leukemia Network guidelines or be intolerant to at least one prior TKI.

All patients were required to have a Lansky performance status of at least 50% (for patients ≤16 years of age) or a Karnofsky performance status of at least 50% (for patients >16 years of age). Adequate bone marrow function, neutrophil count, and renal function are also required. Patients were excluded if they had primary Ph-positive acute lymphoblastic leukemia, had only extramedullary disease, or had documented BCR-ABL1 T315I or V299L mutations.

In a phase 1 trial, bosutinib 400 mg/m2 was administered orally once daily in patients with drug-resistant/intolerant Ph-positive chronic myelogenous leukemia. Once the recommended Phase 2 dose is determined, subsequent patients with resistant/intolerant disease will receive Phase 2 treatment at RP2D. Newly diagnosed patients were enrolled only during Phase 2, during which they received oral bosutinib at 300 mg/m2 once daily.

According to the U.S. Food and Drug Administration (FDA), the recommended dose of bosutinib for children with newly diagnosed Ph-positive chronic myelogenous leukemia is 300 mg/m2, taken orally once a day with food. 1. The recommended dose for children with drug-resistant/intolerant Ph-positive chronic myelogenous leukemia is 400 mg/m2, taken orally once a day with food.

Regarding safety, the most common adverse reactions reported in at least 20% of pediatric patients include diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, liver function abnormalities, headache, pyrexia, decreased appetite, and constipation. The most common laboratory abnormalities worsening from baseline in at least 45% of pediatric patients include increased creatinine, increased alanine aminotransferase, increased aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.

The originator drug of bosutinib is not marketed in the country, so it cannot be included in medical insurance. Currently, the original drugs sold overseas include Turkish version and European version. The price of the Turkish version may be more than RMB 2,000 per box of 500mg*28, and the price of the European version may be more than RMB 30,000 (the price may fluctuate due to the exchange rate). There are also bosutinib generic drugs produced overseas in other countries. Their pharmaceutical ingredients are basically the same as those of the original drug. The price of 500mg*30 per box may be more than 2,000 yuan (the price may fluctuate due to the exchange rate), and the price is relatively cheap.