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HomeAboutAboutMechanism of ActionNCCN Guidelines® Recommendations for CMLTreatment ConsiderationsEfficacyEfficacyAdult: Newly Diagnosed Patients with CP Ph+ CMLBFORE EfficacyBFORE Study DesignAdult: Ph+ CML in Patients with Resistance or Intolerance to Prior TherapyStudy 200 EfficacyStudy 200 Study DesignPediatric: CP Ph+ CML in Patients Who Are Newly Diagnosed or Resistant or Intolerant to Prior TherapyBCHILD EfficacyBCHILD Study DesignSafetySafetyAdult: Newly Diagnosed Patients with CP Ph+ CMLBFORE SafetyAdult: Ph+ CML in Patients with Resistance or Intolerance to Prior TherapyStudy 200 SafetyPediatric: CP Ph+ CML in Patients Who Are Newly Diagnosed or Resistant or Intolerant to Prior TherapyBCHILD SafetyDosingDosingAdult Dosing and AdministrationPediatric Dosing and AdministrationTherapy ManagementSupport & ResourcesSupport & ResourcesEventsMaterialsVideosCo-pay, Access, and Patient SupportDownloadable Resources
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NCCN Guidelines® Recommendations for CMLTreatment and response monitoring recommendations for adult patients

Treatment of CML

Monitoring TKI response

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NCCN Guidelines® in oncology1

Bosutinib (BOSULIF®) is recommended by the NCCN Guidelines® as a primary treatment option for patients with newly diagnosed CML (category 1) and as an option for CML patients in need of 2nd- or later-line TKI therapy (category 2A).

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 December 15, 2023. 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.Pfizer statement: There are no data demonstrating efficacy or safety for bosutinib in second line following dasatinib or nilotinib.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; CML=chronic myelogenous leukemia; CP=chronic phase; 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; TKI=tyrosine kinase inhibitor.ReferenceReferenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.3.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed May 1, 2021. To view the most recent and complete version of the guidelines, go online to NCCN.org.​​ 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.
NCCN Guidelines® for monitoring response in CML1

The following monitoring guidelines provide important information on monitoring the response to TKI therapy in patients with CP CML.

Monitoring with qPCR (IS) every 3 months is recommended for all patients after initiating TKI therapy, including those who meet response milestones at 3, 6, and 12 months (≤10% BCR-ABL1 IS at 3 and 6 months, ≤1% BCR-ABL1 IS at 12 months, and ≤0.1% BCR-ABL1 IS at >12 months). After CCyR (≤1% BCR-ABL1 IS) has been achieved, molecular monitoring is recommended every 3 months for 2 years and every 3 to 6 months thereafter.

Treatment options based on BCR-ABL1 mutation profile1

Patients with disease resistant to primary treatment with imatinib should be treated with bosutinib, dasatinib, or nilotinib in the second-line setting, taking into account BCR-ABL1 mutation status.

Patients with disease resistant to primary treatment with bosutinib, dasatinib, or nilotinib can be treated with an alternate TKI (other than imatinib) in the second-line setting, taking into account BCR-ABL1 mutation status. The durability of these responses is frequently limited.

The table below lists the BCR-ABL1 mutations that should NOT be treated with bosutinib, dasatinib, or nilotinib in the second-line setting.

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 December 15, 2023. 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.

For more CML monitoring guidance, please reference the full NCCN Clinical Practice Guidelines in Oncology for Chronic Myeloid Leukemia at NCCN.org.

See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020, p CML-C, for complete details.See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020, p CML-D, for definitions of response milestones.BCR-ABL1 0.1% at 12 months is associated with a very low probability of subsequent disease progression and a high likelihood of achieving a subsequent MR4, which may facilitate discontinuation of TKI therapy.Patients with BCR-ABL1 only slightly >10% at 3 months and/or with a steep decline from baseline may achieve <10% at 6 months and have generally favorable outcomes. Therefore, it is important to interpret the value at 3 months in this context before making drastic changes to the treatment strategy.Achievement of response milestones must be interpreted within the clinical context. Patients with more than 50% reduction compared with baseline or minimally above the 10% cutoff can continue the same dose of dasatinib, nilotinib, or bosutinib for another 3 months. Continuation of imatinib 400 mg is not recommended.Discontinuation of TKI with careful monitoring is feasible in selected patients. See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020, p CML-E, for complete details.Mutations contraindicated for imatinib are too numerous to include. There are compound mutations that can cause resistance to ponatinib, but those are uncommon following treatment with bosutinib, dasatinib, or nilotinib.Bosutinib has minimal activity against F317L mutation. Nilotinib may be preferred over bosutinib in patients with F317L mutation.Ponatinib is a treatment option for patients with T315I mutation and/or patients for whom no other TKI is indicated.Omacetaxine is a treatment option for patients with disease that is resistant and/or intolerant to 2 or more TKIs.BCR-ABL=breakpoint cluster region-Abelson; CCyR=complete cytogenetic response; CML=chronic myelogenous leukemia; CP=chronic phase; HCT=hematopoietic stem cell transplant; IS=international scale; MCyR=major cytogenetic response; MR=molecular response; NCCN=National Comprehensive Cancer Network; qPCR=quantitative polymerase chain reaction; TKI=tyrosine kinase inhibitor.ReferenceReferenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed April 8, 2020. To view the most recent and complete version of the guidelines, go online to NCCN.org. 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.
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INDICATIONSBOSULIF is indicated for the treatment of:

  • Adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy 

  • Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy
Important Safety Information 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 adults 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 adults 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). Among 49 pediatric patients with CP Ph+ CML that was newly diagnosed or resistant or intolerant to prior therapy, the median time to onset of diarrhea (all grades) was 2 days, median duration was 2 days, and the median number of episodes was 2 (range, 1–198). 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: In adults with mild, moderate, or severe hepatic impairment, the recommended starting dose is 200 mg daily. BOSULIF may cause elevations in serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). Out of 1711 adults in BOSULIF clinical trials, 2 cases consistent with drug-induced liver injury have occurred without alternative causes. In the study of adults with newly diagnosed CP Ph+ CML, the incidence of ALT and AST elevations was 68% and 56%, respectively. In adults with CML who were resistant or intolerant to prior therapy, the incidence of ALT and AST elevations was 53% and 47%, respectively; 60% of these patients experienced an increase in either ALT or AST. Among 49 pediatric patients with CP Ph+ CML that was newly diagnosed or resistant or intolerant to prior therapy, the incidence of ALT and AST elevations was 59% and 51%, respectively; 76% of 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.  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 adults than in those 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 adults and in those with newly diagnosed CML and were more common in adults 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 adults with newly diagnosed CML, cardiac failure occurred in 1.9% of adults treated with BOSULIF compared to 0.8% of those treated with imatinib. Cardiac ischemic events occurred in 4.9% of adults treated with BOSULIF compared to 0.8% of those treated with imatinib. In a single-arm study of adults 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. Among 49 pediatric patients with CP Ph+ CML that was newly diagnosed or resistant or intolerant to prior therapy, 4 patients (8%) had Grade 1-2 cardiac events, including tachycardia (n=2), angina pectoris, right bundle branch block, and sinus tachycardia (n=1 each). 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 (≥20%), in adult and pediatric patients with CML are diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, respiratory tract infection, and constipation. The most common laboratory abnormalities (≥20%) in adult and pediatric patients are creatinine increased, hemoglobin decreased, lymphocyte count decreased, platelets decreased, ALT increased, calcium decreased, white blood cell count decreased, AST increased, absolute neutrophil count decreased, glucose increased, phosphorus decreased, urate increased, alkaline phosphatase increased, lipase increased, creatine kinase increased, and amylase increased. 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. Indications

BOSULIF is indicated for the treatment of:

  • Adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy 

  • Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy
 Please see full Prescribing Information.