Chronic myeloid leukemia is a malignant disease of the bone marrow in which too many white blood cells are produced. In most patients, a genetic alteration of the Philadelphia chromosome can be detected. As first-line therapy, the tyrosine kinase inhibitor bosutinib is convincing.
A subtype of myeloproliferative neoplasms, chronic myeloid leukemia (CLL) is characterized by uncontrolled proliferation of granulocytes. It is not uncommon for up to 500,000 leukocytes per microliter of blood to be measured at diagnosis. Blood clots or vascular occlusions can result. In most cases, the disease recruits from a fusion of the ABL1 and BCR genes. The resulting Philadelphia chromosome can be detected in almost all CML patients. However, the resulting fusion gene, the tyrosine kinase BCR-ABL1, is impaired in its function, leading to uncontrolled growth and proliferation of granulocytes. Symptoms usually develop very slowly and are rather nonspecific (tab. 1) . Therefore, it is not surprising that the disease is often discovered by an incidental finding.
First-line therapy with TKI
Current guidelines recommend first-line treatment of CML in chronic phase with a tyrosine kinase inhibitor (TKI). If the response is insufficient or resistance develops, a TKI switch is recommended (Tab. 2). The second-generation TKI bosutinib (Bosulif®) inhibits BCT-ABL1, among others, and can thus curb the proliferation of CML cells. In a randomized phase III trial, 536 patients with newly diagnosed CML in chronic phase were randomized 1:1 to receive either 400 mg of bosutinib or the same amount of imatinib daily. At 12 months, there was a good molecular response (MMR) of 68.7% vs. 59.3%. After 24 months, this increased again to 61.2% vs. 50.7%. In addition, a significantly faster response was demonstrated. Deep molecular remission (MR) was also more pronounced, 39.9% vs. 31.3% in the bosutinib group.
The most common side effects of all grades were increased ALT, fatigue, and upper respiratory tract infections. The latter two AEs occurred with comparable frequency in both groups. To achieve an appropriate balance between efficacy and safety, dose adjustments can and should be made. This is essential, especially against the background of long-term treatment.
Source: Pfizer
Further reading:
- Cortes JE, et al: Bosutinib vs imatinib for newly diagnosed chronic myeloid leukemia in the BEFORE trial 24 month follow-up. Journal of Clinical Oncology 2018; 36(3): 231-237.
InFo ONCOLOGY & HEMATOLOGY 2019; 7(6): 43 (published 9/12/19, ahead of print).
