Bosutinib Therapy in Patients With Chronic Myeloid Leukemia: Practical Considerations for Management of Side Effects

Abstract

The past decade has witnessed great advances in the treatment of chronic myeloid leukemia (CML), brought about in large part by the development of BCR-ABL tyrosine kinase inhibitors (TKIs). Bosutinib joins the armamentarium of approved TKIs for the treatment of chronic phase (CP), accelerated phase (AP), and blast phase (BP) Philadelphia chromosome (Ph)-positive CML resistant to or intolerant of prior therapy. Bosutinib has an adverse-event (AE) profile distinct from that of other TKIs. Diarrhea is the predominant toxicity associated with bosutinib treatment; other commonly reported nonhematologic AEs include rash and liver enzyme elevations. Cardiac events, fluid retention, and electrolyte abnormalities are infrequent. Optimal response to bosutinib requires adherence, which depends, in part, upon optimal management of associated toxicities. The oncology clinician can facilitate this process by providing patient education, timely patient follow-up, and close monitoring to promptly identify and manage AEs. Thus, optimal patient management requires a thorough and current understanding of toxicity profiles and AE management paradigms. This review provides an overview of bosutinib safety data derived from ongoing clinical trials and offers practical clinical strategies currently used to manage toxicities associated with bosutinib treatment in patients with Ph-positive CP, AP, and BP CML.

HDAC6—An Emerging Target Against Chronic Myeloid Leukemia?

“…Data from a phase II study suggest an increased incidence of arterial thrombotic events in patients receiving ponatinib, thus ending a phase III study. In addition, third generation TKIs do not escape the appearance of resistance phenomena [5,62]. Third generation TKIs also include radotinib, a TKI with structural similarities to imatinib and nilotinib, which was approved in Korea in 2012 for the second-line treatment of CML [73].…”

Fluid retention-associated adverse events in patients treated with BCR::ABL1 inhibitors based on FDA Adverse Event Reporting System (FAERS): a retrospective pharmacovigilance study

“…Pericardial effusion sometimes occurred concomitantly, with 26.9% of patients taking dasatinib reported to have pleural effusion and also pericardial effusion 27. Less frequent occurrences have been observed in patients treated with bosutinib, but if used after dasatinib treatment, the proportion of pleural effusion during bosutinib treatment increases 28–30. Pleural effusions had been observed in 5–15% of patients after prolonged exposure to bosutinib 31.…”

“…27 Less frequent occurrences have been observed in patients treated with bosutinib, but if used after dasatinib treatment, the proportion of pleural effusion during bosutinib treatment increases. [28][29][30] Pleural effusions had been observed in 5-15% of patients after prolonged exposure to bosutinib. 31 Fluid retention events associated with nilotinib, such as pleural effusion, pericardial effusion and pulmonary oedema, were reported uncommon (<4% of patients) in the ENESTnd 10-year analysis.…”

The Role of Bosutinib in Chronic Myeloid Leukemia: An Indian Perspective

“…A study by Ault et al suggests comprehensive skincare and the use of topical agents, immunomodulatory agents, or systemic antibiotics for severe cases. 39 Diarrhea was reported as the most common AE in the Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia (BELA) trial (67.7% patients), 20 BFORE trial (70.1% patients), 19 and in a recent real-world study on bosutinib (55% patients). 29 Myelosuppression was comparable between bosutinib and imatinib arm in the BFORE trial (45.5 vs. 43.4%) 19 and BELA trial, where the incidence of thrombocytopenia was experienced in a similar percentage of patients (28 vs. 28%) as was the incidence of anemia (25 vs. 23%), while the incidence of neutropenia was lower in the bosutinib versus the imatinib arm (13 vs. 30%).…”