Therapy management

Management considerations for selected adverse reactions associated with BOSULIF

Diarrhea

Cases of diarrhea occurred early in treatment, with frequency and severity typically lessening over time1
70% of newly diagnosed adults with CP Ph+ CML experienced diarrhea2
8% experienced grade 3/4 diarrhea
85% of CP CML patients with resistance or intolerance to prior therapy experienced diarrhea2
9% experienced grade 3/4 diarrhea
76% of AdvP CML patients with resistance or intolerance to prior therapy experienced diarrhea2
4% experienced grade 3/4 diarrhea
Management strategies for diarrhea1
Diarrhea, nausea, vomiting, and abdominal pain occur with BOSULIF. Monitor and manage patients using standards of care, including:
Dose adjustments for diarrhea1
Withhold, dose reduce, or discontinue BOSULIF as necessary
Communication to patients4
Diet modifications may help limit diarrhea, such as avoiding:
Advise patients to seek medical attention promptly if symptoms persist.
AdvP=advanced phase; AR=adverse reaction; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; Ph+=Philadelphia chromosome–positive.

Liver enzyme elevations

In newly diagnosed patients1
The incidence of ALT elevation was 31%, and AST elevation was 23%; the incidence of grade 3/4 elevations was 19% and 10%, respectively
Of patients who experienced transaminase elevations of any grade, 79% experienced their first event within the first 3 months
The median time to onset of increased ALT and AST was 32 and 43 days, respectively, and the median duration was 20 and 15 days, respectively
In patients with resistance or intolerance to prior therapy1
20% of patients experienced an increase in either ALT or AST
Most cases of transaminase elevations occurred early in treatment
Of patients who experienced transaminase elevations of any grade, more than 80% experienced their first event within the first 3 months
The median time to onset of increased ALT and AST was 35 and 33 days, respectively, and the median duration for each was 21 days
Perform monthly hepatic enzyme tests for the first 3 months of treatment with BOSULIF and as clinically indicated. In patients with transaminase elevations, liver enzymes should be monitored more frequently.1
Dose adjustments for elevated liver transaminases1
Communication to patients1
Advise patients of the possibility of developing liver function abnormalities and to immediately report jaundice
ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; Ph+=Philadelphia chromosome–positive; ULN=upper limit of normal.

Myelosuppression

Thrombocytopenia, anemia, and neutropenia occur with BOSULIF treatment1
Perform complete blood counts weekly for the first month of therapy and then monthly thereafter, or as clinically indicated1
To manage myelosuppression, withhold, dose reduce, or discontinue BOSULIF as necessary1
Dose adjustments for myelosuppression: neutropenia and thrombocytopenia
Communication to patients1
Advise patients of the possibility of developing low blood cell counts and to immediately report fever, any suggestion of infection, or signs or symptoms suggestive of bleeding or easy bruising
ANC=absolute neutrophil count; AR=adverse reaction; Ph+=Philadelphia chromosome–positive.

Fluid retention

Fluid retention occurs with BOSULIF and may cause pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema1
Monitor and manage patients using standards of care1
Dose adjustments for fluid retention1
Interrupt, dose reduce, or discontinue BOSULIF as necessary
Communication to patients1
Advise patients of the possibility of developing fluid retention (swelling, weight gain, or shortness of breath) and to seek medical attention promptly if these symptoms arise
AR=adverse reaction; Ph+=Philadelphia chromosome–positive.
Expert Panel review
Management of AEs for bosutinib
In 2018, an expert review panel of 7 hematologists discussing how they use BOSULIF as 1L or ≥2L in patients with CP-CML was published in the Journal of Hematology & Oncology. The full article, “Management of Adverse Events Associated With Bosutinib Treatment of Chronic-Phase Chronic Myeloid Leukemia: Expert Panel Review,” can be viewed on the journal site, linked below. A guide highlighting key takeaways is also available here for download. The FDA has not reviewed the recommendations contained in this reprint.
AE=adverse event.
References
1.
Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231-237.
2.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
3.
Data on file. Pfizer Inc, New York, NY.
4.
Leukemia & Lymphoma Society. Digestive disorders. http://www.lls.org/treatment/managing-side-effects/digestive-disorders. Accessed March 6, 2020.
Reference
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.