Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

Abstract

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs. Additional BYOND Study Investigators are listed below Acknowledgements.

Bosutinib in the real‐life treatment of chronic myeloid leukemia patients aged >65 years resistant/intolerant to previous tyrosine‐kinase inhibitors

“…However, most of the published studies evaluated patients with a lower median age than the median generally observed in clinical practice, so data on elderly subjects are lacking. For example, in the recently published BYOND trial, less than 40% of enrolled patients were aged >65 years 13 . As a consequence, detailed data on the pros and cons of bosutinib use and management in the elderly are scanty, and the present study, so far as we know, is the first report specifically addressing this issue in a large real‐life cohort of unselected elderly patients.…”

“…Bosutinib has shown to be effective in CML patients in the frontline setting and also in second or subsequent lines of treatment 11–13,21,22 : in addition, sponsored trials showed that the main side effects are diarrhea and other gastrointestinal events, are generally mild and manageable, and the safety profile regarding cardiovascular, metabolic, and pulmonary adverse events is favorable 23–27 . These data led to the approval of bosutinib for the treatment of CML patients showing intolerance/resistance to at least two TKIs or as second line in patients not eligible for other TKIs due to comorbidities 28,29 …”

“…Bosutinib is a second‐generation TKI that is active in CML patients resistant or intolerant to frontline imatinib, dasatinib, or nilotinib 11–13 ; the favorable cardiovascular toxicity profile makes bosutinib potentially useful in elderly patients, but at present, no data have been reported in this subset of patients.…”

Safety and efficacy of asciminib treatment in chronic myeloid leukemia patients in real-life clinical practice

“…Intolerant patients are usually managed successfully with alternative second-generation tyrosine-kinase inhibitors (2GTKIs). However, more than half of the patients will eventually discontinue second-line treatment due to loss of response or toxicity 4,5 . Ponatinib is an effective drug in the setting of resistance to 2GTKIs, however with life-threatening side effects and varying responses [6][7][8] .…”

Dual Kinase Targeting in Leukemia

“…In clinical trials on the treatment of chronic phase CML, bosutinib has shown durable efficacy and manageable toxicity in patients resistant or intolerant to imatinib [ 123 ] and achieved higher and faster molecular response than imatinib as a first-line treatment [ 124 ]. Accordingly, bosutinib was first approved in 2012 for the treatment of resistant CML [ 125 ] and in 2017 for first-line treatment of chronic phase CML [ 96 , 126 ].…”