Bosutinib: Management of Adverse Events in Chronic Myeloid Leukemia
Managing adverse effects after starting a TKI can be challenging, and health care practitioners often look to CML experts for guidance.
Bosutinib is a BCR-ABL-directed tyrosine kinase inhibitor (TKI) that is approved by the US Food and Drug Administration for use in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).1 This includes patients that are both newly diagnosed as being in chronic phase or those who are resistant or intolerant to prior treatments. Bosutinib is dosed based on indication — typically the dose ranges from 400 mg to 600 mg by mouth daily — and it should be taken with food. Regardless of the indication, bosutinib needs to be renally dose-adjusted for creatinine clearance of less than or equal to 50 mL/minute.
Bosutinib is primarily metabolized by CYP450 3A4, therefore, a thorough medication reconciliation should be performed prior to initiation and when new medications are added to a regimen. It is recommended that bosutinib not be used with medications with moderate to strong inhibition of CYP3A4 to avoid increased levels of bosutinib, which could lead to increased toxicities.1
Bosutinib is among the 5 available TKIs used in CML, which also include imatinib, nilotinib, ponatinib, and dasatanib.2 As a class, TKIs have been linked to various adverse events. Each agent has its own set of side effects; however, the more common major class-wide toxicities include gastrointestinal disorders (nausea, vomiting, diarrhea, liver toxicity, pancreatitis) and cardiopulmonary issues (QTc prolongation, heart failure, hypertension, thrombosis, pulmonary hypertension, pneumonitis, pleural effusions, and hyperlipidemia). Adverse events reported in at least 20% of patients include gastrointestinal issues, cardiopulmonary problems, hematological dysfunctions (leukopenia, anemia, thrombocytopenia, neutropenia), dermatological reactions (rash), and miscellaneous events (fever, fatigue, headache).1
When choosing a TKI, the medication should be tailored to each individual patient, including an evaluation of the potential for increased risk of adverse events, drug-drug interactions and comorbidities.
Managing adverse effects after starting a TKI can be challenging and health care practitioners often look to CML experts for guidance. Recently, an expert panel of 7 hematologists met to better summarize and recommend the best approaches to managing adverse events in patients taking bosutinib.2
Cortes and colleagues provided an algorithm to follow regarding dose initiation in patients.2 A patient's CML disease risk can be assessed using the Sokal score, which utilizes 4 variables: age, spleen size, platelet count, and percentage of myeloblasts.3,4 Disease risk is considered high when the Sokal score is more than 1.2, intermediate when it is between 0.80 and 1.20, and low when it is less than 0.80.3,4 Patients with high disease risk usually require a rapid response, therefore, the dosing may be more aggressive in these cases. Low-risk patients may start with lower-dose regimens, with dose escalations planned for future treatment.
When evaluating a patient for the individual's potential for an adverse event related to bosutinib administration, it is important to review their disease risk, whether the bosutinib is being used as a first- or second-line (or beyond) agent, and what type of side effects they have experienced while receiving prior TKIs.