Introduction

Bosutinib (trade name: Bosulif) has been approved in Germany since March 2013 for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in adults who have had treatment before. Since May 2018, the drug has also been approved for the first-line treatment of the chronic phase in people with newly diagnosed chronic myeloid leukemia.

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, usually develops from a mutated chromosome called the Philadelphia chromosome. The medical term for this condition is Philadelphia chromosome-positive CML (Ph+ CML). CML is a type of bone marrow cancer in which the bone marrow makes too many granulocytes and blast cells (immature granulocytes) which then enter the blood. Granulocytes are a type of white blood cell and an important part of the immune system.

Because the condition progresses very slowly over years, it can go unnoticed for a long time. There are three phases:

Chronic phase: This phase is almost always symptom-free. That's why the condition is usually discovered by chance during routine blood examinations.

Accelerated phase: As CML progresses, blood test results get worse. Blast cell counts increase and patients look pale, feel tired and are less fit.

Blast crisis: In this far advanced phase, more and more blast cells are made in the bone marrow. This also slows down the production of red blood cells (erythrocytes) and platelets (thrombocytes). The effects of a blast crisis include susceptibility to infections, anemia, and poor blood clotting. Blast crises are life-threatening.

Bosutinib inhibits various proteins that cause bone marrow to make more granulocytes and blast cells. The aim of treatment with this drug is to stop the progression of CML in this way.

Application

Bosutinib is available in tablet form in three doses (100, 400 and 500 mg). The tablet is taken once a day with a meal. The dose depends on the phase of the illness, the side effects that arise, and the results of regular blood tests. It shouldn't exceed 600 mg per day, though. If the side effects become too severe, the treatment is stopped.

Other treatments

For adults with the Philadelphia chromosome and newly diagnosed CML who have not had treatment before, the first-line treatment options in the chronic phase include drugs such as imatinib, nilotinib, or dasatinib.

For people who have had treatment before, ponatinib or interferon-alpha may be used, depending on the phase of the illness.

Assessment

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) wanted to find out whether bosutinib has any advantages or disadvantages for adults in the chronic phase of newly diagnosed Ph+ CML when compared with the current standard treatments.

The manufacturer provided data from an ongoing study in 2018, involving only people who had not had treatment before. Of those 487 adults, half received bosutinib, and the other half had treatment with imatinib. After at least two years, the study showed the following results in these patients:

What are the advantages of bosutinib?

  • Edemas: The study suggests that bosutinib has an advantage here. Edemas developed in about 13 out of 100 people in the bosutinib group, compared to 41 out of 100 people in the group with the standard treatment.
  • Diseases of the skeletal muscles, connective tissue and bones: Here too, the results of the study suggest that bosutinib has an advantage. About 34 out of 100 people who took bosutinib had such side effects. In the standard treatment group, these side effects occurred in 59 out of 100 people.

What are the disadvantages of bosutinib?

  • Serious side effects: The study suggests that bosutinib has a disadvantage here compared with the standard treatment. Severe side effects occurred earlier and more often with bosutinib: in 65 out of 100 people compared to 48 out of 100 people with the standard treatment.
  • Severe heart problems: Here too, the study suggests that bosutinib has a disadvantage. About 4 out of 100 people who took bosutinib had severe heart problems. In the comparison group, only about 1 out of 100 people had these side effects.
  • Severe diarrhea: Severe diarrhea occurred in 8 out of 100 people who took bosutinib, and in only about 1 out of 100 people who had the standard treatment.
  • The study also suggests that bosutinib has a disadvantage concerning the following side effects:
    • Severe platelet deficiency (thrombocytopenia)
    • Severe liver dysfunction
    • Gastrointestinal (stomach and bowel) problems
    • Rashes

No difference

  • No difference was found in terms of the following:
    • Life expectancy
    • Health-related quality of life
    • General health
  • There was also no relevant difference concerning treatments stopped due to side effects.

What remains unanswered?

  • Progression of the condition to blast crisis: The manufacturer didn't provide any usable data regarding the question of whether bosutinib can prevent the condition from progressing.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of this review and the hearings received, the G-BA passed a resolution on the added benefit of bosutinib (Bosulif) as first-line treatment and as subsequent treatment.