Practical considerations in the management of patients treated with bosutinib for chronic myeloid leukemia

Bosutinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemia (CML), and for patients with Ph + chronic phase, accelerated phase, or blast phase CML resistant or intolerant to prior therapy. As is the case for all TKIs approved for treatment of CML, bosutinib is associated with adverse events (AEs) that require appropriate management to ensure adherence to treatment and optimized outcomes. The aim of this review is to provide physicians with updated practical information for the prevention and management of AEs occurring during treatment with bosutinib, including dosing strategies, based on the latest published evidence and clinical experience. Clinical studies and real-world evidence have shown bosutinib has a generally favorable safety profile, which has remained consistent across lines of therapy and in long-term reports. Adjusting the starting dose and/or modifying the dose during treatment with bosutinib are important strategies to manage AEs and improve tolerability, which are recognized within the label and in treatment guidelines. Dosing adjustment strategies to manage AEs are a recognized management approach for other TKIs in the treatment of CML and are not exclusive to bosutinib. In summary, long-term results from clinical trials and emerging real-world evidence demonstrate bosutinib has a safety profile that can largely be managed with treatment modifications and/or supportive care. Increased experience in managing toxicities and by using a personalized dosing approach may further improve adherence and outcomes with bosutinib. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-024-05851-4.

• The review provides practical recommendations for how to stop and manage side effects experienced by some people taking bosutinib.
• There is some doable advice your doctor can give you to stop side effects.They can also advise you to identify the signs and symptoms.
• This review may help doctors treating people with CML taking bosutinib manage their side effects and continue bosutinib treatment.

Date of summary: tbd 2023
The full title of this article: Practical considerations in the management of patients treated with bosutinib for chronic myeloid leukemia.

Additional information
More information can be found in the scienti c article of this study, which you can access here: View Scientifi c Article What did this review look at?
• This review looked at useful advice for patients and doctors about how to prevent and manage possible side effects experienced when taking bosutinib.
What is chronic myeloid leukemia?
• Chronic myeloid leukemia (CML) is a type of cancer that affects white blood cells.
-Leukemia cells are abnormal white blood cells.
-Chronic means that it tends to grow slowly over many years.
• CML is caused by the formation of an abnormal fusion gene called BCR-ABL1.
-A fusion gene is made by joining parts of 2 different genes into a completely new gene.
 Genes are parts of DNA that are found in structures called chromosomes.They are found in every cell of the body.
 DNA is a molecule in a person's cells that tells the cells how to work.
 Chromosomes are bundles of DNA.
 The BCR-ABL1 gene is an example of a fusion gene.• The BCR-ABL1 gene is found in the Philadelphia chromosome.It is present in some types of leukemia cancer cells and absent in healthy cells.

What is bosutinib?
• Bosutinib is a type of medicine known as a tyrosine kinase inhibitor (TKI).
-Tyrosine kinases are proteins in the body that manage how cells grow and divide.
-The BCR-ABL1 gene makes a tyrosine kinase that is more active than normal.This makes leukemia cells grow faster than healthy cells.
-Bosutinib works by blocking this more active tyrosine kinase in the leukemia cells, causing those cells to die.
• Bosutinib is taken by mouth daily.
• Bosutinib is an approved treatment for people who have: -CML who have not yet received treatment with a TKI (called newly diagnosed CML).
-CML that is not responding to treatment with other TKIs (such as imatinib, dasatinib, and nilotinib) any longer.
-Stopped their earlier treatment because they could not tolerate side effects.

Additional information
More information can be found in the scienti c article of this study, which you can access here: What was the aim of this review?
• The review looked at information from several clinical and real-world studies of people taking bosutinib for CML.The writers of the review are doctors treating people with CML who are taking bosutinib.
• The review focused on the side effects that some people have experienced when receiving bosutinib.It gives practical advice about how doctors can stop or manage the side effects.
-A side effect is something (expected or unexpected) that you feel was caused by a medicine or treatment you take.
• The authors looked at side effects affecting blood cells, side effects experienced by people taking all TKI medications (affecting the heart, veins, arteries, kidneys, and skin), and side effects experienced by people taking bosutinib (affecting the stomach and intestines, liver, and build-up of uid around the lungs).
• This summary describes practical advice from the writers of the review about how to stop and manage speci c side effects experienced by some people when taking bosutinib.It also includes how to adjust the amount of bosutinib.
What practical advice was given in the review?
Suggestions for preventing and managing side effects

Blood cells • Side effects:
Low levels of some blood cells are common and can occur early during bosutinib treatment, usually within the rst year.Examples include: -Low levels of platelets, which help stop bleeding -Low levels of neutrophils, a type of white blood cell that helps ght infections.

What can you do?
• Look out for the signs and symptoms of these types of side effects: -Unexpected bruising -Fever and signs of infection -Unexpected bleeding -Blood in urine or blood in stool.
• Tell your doctor as soon as possible if you experience these types of side effects.

What can your doctor do?
• Regular blood tests to monitor changes in your blood cells • If these side effects occur: -Lower the dose of bosutinib or pause bosutinib treatment until the levels of blood cells return to normal.
-Keep the dose of bosutinib low if levels of blood cells stay low.
-Treat the low levels of blood cells with other medications.
-Some people will need to stop taking bosutinib.

Additional information
More information can be found in the scienti c article of this study, which you can access here: View Scientifi c Article Heart, veins, and arteries

• Side effects:
Changes that affect the beating of the heart and/or circulation of blood

What can you do?
• Tell your doctor before starting bosutinib treatment if you have conditions affecting your heart or blood circulation.
• Talk to your doctor about possible lifestyle changes that might lower your risk factors for conditions affecting the heart and blood circulation.
• Look out for the signs and symptoms of the following side effects: -Fast, slow, or irregular heartbeat -Chest pain -High blood pressure (signs like headaches, nosebleeds, or fast heartbeat).
• Tell your doctor as soon as possible if you experience these types of side effects.

What can your doctor do?
• Assess and manage your individual risk factors for conditions affecting the heart and blood circulation.
• Speak with a cardiologist for more guidance for people with existing conditions affecting the heart and blood circulation or people at high risk of developing these types of side effects.
• Regular blood tests to monitor levels of electrolytes -Electrolytes are salts and minerals found in the blood that conduct electrical impulses in the body.
• Regular electrocardiograms for people with certain risk factors or conditions -An electrocardiogram checks your heart's rhythm and electrical activity.
• Look at the other medications that you take and how they might affect your heart and blood circulation and how they might change the way bosutinib works.
-Some medications that you take might need to be adjusted or changed when you start bosutinib treatment.
• Start some people on a lower dose of bosutinib.
• If these side effects occur: -Look at all factors that might affect how your heart and blood circulation work, including other medications and your personal risk factors and lifestyle.
-Lower the dose of bosutinib or pause bosutinib treatment until there are no more side effects.
-Treat the side effects affecting the heart and blood circulation with other medications.
-Some people will need to stop taking bosutinib.

Additional information
More information can be found in the scienti c article of this study, which you can access here: View Scientifi c Article

Kidneys • Side effects:
Changes that affect how well your kidneys work

What can you do?
• Tell your doctor before starting bosutinib treatment if you have conditions affecting your kidney.s • Look out for the signs and symptoms of the following side effects: -Needing to urinate more often than usual.
-Urinating less often than usual.
• Keep looking out for these signs and symptoms even if you have been taking bosutinib for a long time.
• Tell your doctor as soon as possible if you experience these side effects.

What can your doctor do?
• Test blood levels of creatinine before starting bosutinib treatment.
-Creatinine is a waste product that is released into the blood by muscles and is cleared out by the kidneys.
-How much creatinine is in your blood tells the doctor how well your kidneys are working.
• Start people on a lower dose of bosutinib if their kidneys are not working as well as they should.
• Continue regular blood tests of creatinine levels.
• If these side effects occur: -Look at all factors that might affect how your kidneys work, including other medications and your personal risk factors.
-Lower the dose of bosutinib or pause bosutinib treatment until there are no more side effects.
-Treat the side effects affecting the kidneys with other medications.
-Some people will need to stop taking bosutinib.

Additional information
More information can be found in the scienti c article of this study, which you can access here: View Scientifi c Article

Skin
• Side effects: Changes that affect how your skin feels and looks

What can you do?
• Tell your doctor before starting bosutinib treatment if you have conditions affecting your skin.
• Look out for the signs and symptoms of the following side effects: -Rash -Itching -Acne.
• Tell your doctor as soon as possible if you experience these types of side effects.
• Keep your skin as healthy as possible: -Avoid long, hot baths -Drink plenty of water.

What can your doctor do?
• If these side effects occur: -Treat the side effects affecting the skin with creams, ointments, or other medications.
-Lower the dose of bosutinib or pause bosutinib treatment until recovery of side effects.
-Some people will need to stop taking bosutinib.• Always take bosutinib tablets with food and water.
• Drink plenty of water.
• Avoid foods that might make you feel worse.
• Look out for the signs and symptoms of the following side effects, even from the rst days after starting bosutinib treatment: -Diarrhea -Nausea -Vomiting -Pain in the stomach.
• Tell your doctor as soon as possible if you experience these types of side effects.

What can your doctor do?
• Check on how you're feeling, especially early in treatment, so they can help you manage these symptoms as soon as possible.
• If these side effects occur: -Treat the side effects with other medications, like anti-nausea or antidiarrheal medications, and uid replacement and advise on how best to take these medications while on bosutinib treatment.
-Lower the dose of bosutinib or pause bosutinib treatment until there are no more side effects.
-Some people will need to stop taking bosutinib.