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by Dr. C.H. Weaver M.D. updated 3/2020

On December 19, 2017, the Food and Drug Administration granted accelerated approval to Bosulif (bosutinib) for treatment of patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML).

About Chronic Myeloid Leukemia (CML)

Chronic myelogenous leukemia is a rare blood cancer, which begins in the bone marrow, but often moves into the blood.(1) Researchers estimate that by 2020, more than 412,000 people worldwide will be diagnosed with leukemia (all types).(2) CML accounts for 10-15% of all incident leukemia cases.(1,3) In the U.S., approximately 48,000 people are living with CML.(4) Around 9,000 new CML cases were diagnosed in the U.S. in 2017.(1)

Recognition of the pivotal role of the BCR-ABL protein in CML led to the development of Gleevec, which blocks the activity of this protein. Gleevec produced high rates of remission among patients with chronic-phase CML and dramatically changed the treatment of this disease. Newer drugs that target the BCR-ABL protein include Tasigna® (nilotinib) and Sprycel® (dasatinib). Both Tasigna and Sprycel appear to be superior to Gleevec for the initial treatment of patients with CML and are approved by the FDA for this purpose.

Bosulif is a third-generation tyrosine kinase inhibitor that targets both Abl and Src kinases. Targeting of Src by Bosulif is thought to be important, as over-expression of Src kinases has been associated with resistance to Gleevec.

Bosulif® (bosutinib) is an oral, once-daily, tyrosine kinase inhibitor (TKI), which inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases. In the U.S., BOSULIF (bosutinib) is indicated for the treatment of patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) and for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy (first approved in September 2012).

Newly Diagnosed CML

Approval of Bosulif was based on data from an open-label, randomized, multicenter clinical trial performed in 487 patients with Ph+ newly-diagnosed CP CML who were treated with either Bosulif 400 mg once daily or Gleevec 400 mg once daily. The major efficacy outcome measure was major molecular response (MMR) at 12 months, defined as less than or equal to 0.1% BCR ABL ratio on international scale (corresponding to greater than or equal to 3 log reduction from standardized baseline) with a minimum of 3000 ABL transcripts as assessed by the central laboratory. MMR at 12 months was 47.2% in the Bosulif group compared to 36.9% in the Gleevec treated patients.

  • Cumulative complete cytogenetic remission rates at one year were 77% for bosutinib and 66% for Gleevec.
  • Cumulative major molecular response rates at one year were 47% for bosutinib and 32% for Gleevec.
  • Times to complete cytogenetic remission or a major molecular response were more rapid in the bosutinib group.
  • Transformation to accelerated/blast phase occurred in 2% of patients treated with bosutinib and 4% of patients treated with Gleevec.
  • More patients in the bosutinib group (22%) discontinued drug taking as a result of adverse events compared with 6% in the Gleevec group.
  • Deaths occurred in 1.6% of bosutinib patients compared with 4.8% in the Gleevec group.

About the BFORE Study

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BFORE (Bosutinib trial in First line chronic myelogenous leukemia tREatment) is a randomized, multicenter, open-label Phase 3 study designed to assess the effectiveness and safety of Bosulif® (bosutinib) as a first-line treatment for patients with chronic phase Ph+ CML. The study enrolled 536 patients to receive Bosulif 400 mg or imatinib 400 mg, a standard of care, for the duration of the study.

CML in Accelerated or Blastic Phase

The FDA first approved bosulif in 2012 for treatment of patients with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

The approval of Bosulif was based on the results of a single clinical trial that included 546 adult patients with chronic, accelerated or blast phase CML. All patients had disease that progressed after treatment with imatinib or imatinib followed by dasatinib and/or nilotinib, or who could not tolerate the side effects of prior therapy. All patients in the trial were treated with Bosulif.(5)

The results of the study showed that 34 percent of patients with chronic phase CML who had been previously treated with imatinib achieved a major cytogenetic response (MCyR) within the first 24 weeks of treatment (which was determined to be the benchmark for efficacy). Among patients who achieved MCyR at any time, 52.8 percent had their response last at least 18 months. In evaluating patients previously treated with imatinib followed by dasatinib and/or nilotinib, researchers found that 27 percent of these patients achieved MCyR within the first 24 weeks of treatment. Of those who achieved MCyR at any time, 51.4 percent had their MCyR last at least nine months.

Among patients with accelerated CML previously treated with at least imatinib, 33 percent experienced a complete hematologic response (meaning blood counts returned to the normal range) and 55 percent achieved overall hematologic response (normal blood counts with no evidence of disease) within the first 48 weeks of treatment. Among patients with blast phase CML, 15 percent achieved complete hematologic response and 28 percent achieved overall hematologic response.

The most common side effects observed with Bosulif were diarrhea, nausea, thrombocytopenia (low platelet levels), vomiting, abdominal pain, rash, anemia (low red blood cell count), fever, and fatigue.

The recommended dose and schedule for Bosulif is 500 mg orally once daily with food. Treatment is to be continued until disease progression or patient intolerance.


  1. American Cancer Society. What is Chronic Myeloid Leukemia?. Accessed August 2017.
  2. GLOBOCAN Online Analysis/Prediction.. Accessed December 2017.
  3. Hochhaus, A. Educational Session: Managing Chronic Myeloid Leukemia as a Chronic Disease. American Society of Hematology. 2011; 10: 1.
  4. National Cancer Institute. Surveillance Epidemiology and End Results (SEER) Cancer Stat Facts: Chronic Myeloid Leukemia (CML).. Accessed December 2017.
  5. FDA approves new orphan drug for chronic myelogenous leukemia [FDA News Release]. U.S. Food and Drug Administration website.