Bosutinib: Management of Adverse Events in Chronic Myeloid Leukemia

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Managing adverse effects after starting a TKI can be challenging, and health care practitioners often look to CML experts for guidance.
Managing adverse effects after starting a TKI can be challenging, and health care practitioners often look to CML experts for guidance.

Myelosuppression

Levels of myelosuppression (thrombocytopenia 35%, anemia 19%, neutropenia 11%, leukopenia 6%) were lower in the BFORE trial compared with the subsequent-line study (thrombocytopenia 40%, anemia 27%, neutropenia 18%, leukopenia 10%).2,5 Complete blood counts (CBCs) should be obtained prior to starting bosutinib, then weekly for the first month, and then once per month based on the health care practitioner's (HCPs) judgment. If the patient's cytopenia persists, then dose reduction should be considered. Temporarily stopping bosutinib is only recommended in patients with grade 3 or higher neutropenia or thrombocytopenia, however, the ultimate decision is left to the discretion of the HCP.

Skin Disorders

Rashes were less common in the BFORE trial (19.8%) compared with the subsequent-line study (range, 27.7%-36.3%).2,5 If a patient develops a rash, additional causes such as other medications or environmental factors should be excluded. Patients should stay well hydrated and avoid skin-irritating substances. Topical treatments and antihistamines can be considered for mild rashes, along with a referral to a dermatologist.

Renal Dysfunction

Renal adverse events have not been reported from the BFORE trial; however, other trials have shown between 9% and 13% of patients with renal adverse events, which are typically measured by increases in blood creatinine.6 Renal function should be checked prior to starting bosutinib and intermittently throughout the course of treatment. Nephrotoxic agents should be avoided, and adequate hydration should be promoted. The dose must be adjusted in patients with creatinine clearance 50 mL/min or less.1

Cardiac Events

Cardiac adverse events (including atrial fibrillation, QTc prolongation, additional arrhythmias) were relatively uncommon, in 5.2% of patients enrolled in the BFORE trial.2,5 Prior to initiation of bosutinib, it is recommended to fully evaluate a patient's cardiovascular history and risk. The patient's baseline risk of QTc prolongation should be assessed with a full medication reconciliation, physical exam and baseline electrocardiogram. If there are any concerns about the patient's current cardiovascular history or potential for risk on bosutinib, then they should be considered for a formal cardiology consultation. Hypomagnesemia or hypokalemia on baseline labs should be promptly corrected prior to initiation of bosutinib. Magnesium and potassium levels should be part of the routine lab monitoring for every patient on the medication.

As the clinical data behind bosutinib continue to accumulate, it will be important to review how its associated adverse events are being managed and if recommendations such as those by Cortes and colleagues are being followed. Continuing to follow these patients in the clinic and consistently asking about adverse events and additional medications can help catch these adverse events early and potentially limit their sequelae.

References

  1. Bosulif® [package insert]. New York, NY: Pfizer Inc.; September 2018.  
  2. Cortes JE, Apperley JF, DeAngelo DJ, et al. Management of adverse events associated with bosutinib treatment of chronic-phase chronic myeloid leukemia: expert panel review. J Hematol Oncol. 2018;11(1):143.
  3. Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63(4):789-799.
  4. Pfirrmann M, Lauseker M, Hoffmann VS, Hasford J. Prognostic scores for patients with chronic myeloid leukemia under particular consideration of competing causes of death. Ann Hematol. 2015;94(Suppl 2):S209-S218.
  5. 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.
  6. Cortes JE, Gambacorti-Passerini C, Kim DW, et al. Effects of bosutinib treatment on renal function in patients with Philadelphia chromosome-positive leukemias. Clin Lymphoma Myeloma Leuk. 2017;17(10):684-695 e6.
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