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  • Writer's pictureThe Rare360 Editorial Team

New Hope for Pediatric Patients: Bosutinib's Approval in Treating Chronic Phase Ph+ CML


Mum and little daughter at pediatrician's office

Understanding Ph+ CML

Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) is a common form of chronic myeloid leukemia (CML). It is a type of leukemia, specifically a blood cancer, characterized by the presence of an abnormal chromosome known as the Philadelphia chromosome. This genetic abnormality results from a translocation of genetic material between chromosomes 9 and 22, leading to the formation of a hybrid gene called BCR-ABL1.


The BCR-ABL1 gene produces a protein that plays a crucial role in the development of CML. This protein, often referred to as the BCR-ABL1 fusion protein, causes the overproduction of white blood cells in the bone marrow, leading to the characteristic features of CML. These abnormal white blood cells can accumulate in the blood and various organs, potentially leading to a range of symptoms and complications.


Ph+ CML typically progresses through three phases: chronic phase, accelerated phase, and blast phase. In the chronic phase, the disease progresses slowly, and many individuals can manage it effectively with medication. Most adults are diagnosed in chronic phase, which is the first phase of Ph+ CML. However, if left untreated or inadequately managed, CML can progress to the more advanced and aggressive phases.


FDA Gives Green Light: Bosutinib Approved for Pediatric Patients

In a significant breakthrough, the Food and Drug Administration (FDA) has granted approval for bosutinib to be used in pediatric patients aged one year and older diagnosed with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). The approval includes patients who are newly diagnosed (ND) as well as those resistant or intolerant (R/I) to prior therapy.


The FDA has also approved a new capsule dosage form of bosutinib, available in strengths of 50 mg and 100 mg. For children who have difficulty swallowing capsules, the medication's contents can be mixed with applesauce or yogurt, ensuring easier administration.


Recommended Dosages and Common Side Effects: What to Expect

Per the FDA, the recommended oral dose is 300 mg/m2 once daily with food (orally) for newly diagnosed patients, while for those resistant/intolerant, the recommended dose is 400 mg/m2 once daily with food (orally).


The most common adverse effects (reported in almost 20% of the patients) included diarrhea, vomiting, nausea, abdominal pain, rash, fatigue, headache, hepatic dysfunction, pyrexia, decreased appetite, and constipation.


In a significant proportion of pediatric patients (approximately 45%), certain laboratory values exhibited changes from their baseline levels. These changes were characterized by elevated creatinine, increased levels of alanine aminotransferase, increased aspartate aminotransferase levels, reduced white blood cell counts, and decreased platelet counts. This underscores the critical need for vigilant and consistent monitoring throughout the course of treatment in pediatric patients.


Clinical Trial Success: Data Backing the Approval

The decision to approve bosutinib for pediatric patients was based on results from the BCHILD trial. This study involved pediatric patients between the ages of 1 and 17 with a specific type of leukemia called Ph-positive CML. Some patients were newly diagnosed, while others had previously received treatment.


For the newly diagnosed patients, the trial found that at a follow-up of approximately 14 months, about 76% of them showed a major response, and roughly 71% achieved a complete response. Additionally, around 28% of these patients had a significant molecular response.

For patients who had previously received treatment and were resistant or intolerant to it, at a follow-up of about 23 months, approximately 82% of them experienced a major response, and nearly 79% achieved a complete response. About 50% of these patients showed a significant molecular response.


The BCHILD trial included patients who met specific criteria, such as their age, type of leukemia, and previous treatment history. Patients needed to have a certain level of overall health and adequate bone marrow function, among other requirements.


The study excluded patients with certain conditions, such as primary Ph-positive acute lymphoblastic leukemia or specific genetic mutations. Treatment in the trial involved taking bosutinib at different doses, depending on the phase of the trial and the patient's condition.


This approval marks a significant advancement in the treatment options available for pediatric patients with Ph+ CP-CML, offering new hope and improved outcomes.


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