Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.3.2021. © 2021 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed May 1, 2021. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
*Patients with disease that is resistant to primary treatment with imatinib should be treated with bosutinib, dasatinib, or nilotinib in the second-line setting. Patients with disease that is resistant to primary treatment with bosutinib, dasatinib, or nilotinib could be treated with an alternate TKI (other than imatinib) in the second-line setting, based on BCR-ABL1 mutation profile.
†Based on long-term follow-up data from the DASISION and ENESTnd trials and preliminary data from the BFORE trial, second-generation TKIs (dasatinib, nilotinib, or bosutinib) are preferred for patients with an intermediate- or high-risk score, especially for young women whose goal is to achieve a deep and rapid molecular response and eventual drug discontinuation of TKI therapy for family planning purposes.
‡Imatinib may be preferred for older patients with comorbidities such as cardiovascular disease.
BCR-ABL=breakpoint cluster region-Abelson; BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; DASISION=The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients; ENESTnd=Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients; NCCN=National Comprehensive Cancer Network; Ph+=Philadelphia chromosome–positive; TKI=tyrosine kinase inhibitor.
BOSULIF® (bosutinib) is indicated for the treatment of adult patients with:
Contraindications: History of hypersensitivity to BOSULIF. Reactions have included anaphylaxis.
Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and abdominal pain occur with BOSULIF. In the study of patients with newly diagnosed CP Ph+ CML, the median time to onset for diarrhea (all grades) was 4 days and the median duration per event was 3 days. In the study of patients with CML who were resistant or intolerant to prior therapy, median time to onset of diarrhea (all grades) was 2 days, median duration was 2 days, and the median number of episodes per patient was 3 (range 1-268). Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary.
Myelosuppression: Thrombocytopenia, anemia, and neutropenia occur with BOSULIF. Perform complete blood counts weekly for the first month and then monthly thereafter, or as clinically indicated. Withhold, dose reduce, or discontinue BOSULIF as necessary.
Hepatic Toxicity: BOSULIF may cause elevations in serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). Out of 1711 patients in BOSULIF clinical trials, 2 cases consistent with drug-induced liver injury have occurred without alternative causes. In the study of patients with newly diagnosed CP Ph+ CML, the incidence of ALT and AST elevations was 68% and 56%, respectively. In patients with CML who were resistant or intolerant to prior therapy, the incidence of ALT and AST elevations was 53% and 47%, respectively; sixty percent of these patients experienced an increase in either ALT or AST. Perform hepatic enzyme tests at least monthly for the first 3 months and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Withhold, dose reduce, or discontinue BOSULIF as necessary. In patients with mild, moderate, or severe hepatic impairment, the recommended starting dose is 200 mg daily
Cardiovascular Toxicity: BOSULIF can cause cardiovascular toxicity, including cardiac failure, left ventricular dysfunction, and cardiac ischemic events. Cardiac failure events occurred more frequently in previously treated patients than in patients with newly diagnosed CML and were more frequent in patients with advanced age or risk factors, including previous medical history of cardiac failure. Cardiac ischemic events occurred in both previously treated patients and in patients with newly diagnosed CML and were more common in patients with coronary artery disease risk factors, including history of diabetes, body mass index greater than 30, hypertension, and vascular disorders. In a randomized study of patients with newly diagnosed CML, cardiac failure occurred in 1.9% of patients treated with BOSULIF compared to 0.8% of patients treated with imatinib. Cardiac ischemic events occurred in 4.9% of patients treated with BOSULIF compared to 0.8% of patients treated with imatinib. In a single-arm study of patients with CML who were resistant or intolerant to prior therapy, cardiac failure was observed in 5.3% of patients and cardiac ischemic events were observed in 4.9% of patients treated with BOSULIF. Monitor patients for signs and symptoms consistent with cardiac failure and cardiac ischemia and treat as clinically indicated. Interrupt, dose reduce, or discontinue BOSULIF as necessary.
Fluid Retention: Fluid retention occurs with BOSULIF and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary.
Renal Toxicity: An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF. Monitor renal function at baseline and during therapy, with particular attention to patients with preexisting renal impairment or risk factors for renal dysfunction. Lower starting doses are recommended for patients with renal impairment. For patients who have declining renal function while on BOSULIF or who cannot tolerate the starting dose, follow dose adjustment recommendations for toxicity.
Embryo-Fetal Toxicity: BOSULIF can cause fetal harm. Women of childbearing potential should be advised of the potential risk to the fetus and advised to use effective contraceptive measures while on treatment and for at least 2 weeks after the final dose.
Adverse Reactions: The most common adverse reactions, in ≥20% of patients with newly diagnosed CP Ph+ CML or CP, AP, or BP Ph+ CML with resistance or intolerance to prior therapy (N=814) were diarrhea (80%), rash (44%), nausea (44%), abdominal pain (43%), vomiting (33%), fatigue (33%), hepatic dysfunction (33%), respiratory tract infection (25%), pyrexia (24%), and headache (21%). The most common laboratory abnormalities that worsened from baseline in ≥20% of patients were creatinine increased (93%), hemoglobin decreased (90%), lymphocyte count decreased (72%), platelets decreased (69%), ALT increased (58%), calcium decreased (53%), white blood cell count decreased (52%), absolute neutrophil count decreased (50%), AST increased (50%), glucose increased (46%), phosphorus decreased (44%), urate increased (41%), alkaline phosphatase increased (40%), lipase increased (36%), creatine kinase increased (29%), and amylase increased (24%).
CYP3A Inhibitors and Inducers: Avoid concurrent use with strong or moderate CYP3A inhibitors or strong CYP3A inducers.
Proton Pump Inhibitors (PPIs): Consider using short-acting antacids or H2 blockers instead of PPIs to avoid a reduction in BOSULIF exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.
Lactation: Because of the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment with BOSULIF and for at least 2 weeks after the last dose.
BOSULIF is indicated for the treatment of adult patients with:
Please see full Prescribing Information.