Bosutinib a Good Fourth-Line Option in CML

Ball-and-stick model of bosutinib

A small retrospective study of heavily pretreated patients with chronic myeloid leukemia (CML) found bosutinib to be a good option in the fourth-line setting.

The results of the study were published in the American Journal of Hematology, by Valentín García-Gutíerrez, of the Hospital Universitario Ramón y Cajal in Madrid, and colleagues.

The tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, and nilotinib are currently the three approved first-line treatments for CML, so most patients will receive bosutinib as a fourth-line therapy, according to the authors.

There is very little data on bosutinib for CML in this setting, however. In a phase I/II study of CML patients treated with bosutinib, only 3 out of 188 patients were treated with bosutinib in the fourth-line setting. “The aim of this study was to fill this gap, and analyze the efficacy and safety of fourth-line bosutinib treatment after failure or intolerance to imatinib, dasatinib, and nilotinib,” wrote the authors.

The researchers reviewed the records of 30 chronic-phase CML patients who had relapsed or were intolerant to imatinib, nilotinib, and dasatinib. Patients studied had all received 500 mg bosutinib daily, with dose adjustments made according to physician judgment. With a median follow-up time of 11.5 months, 17 patients (56.6%) were able to achieve or maintain complete cytogenetic response (CCyR) and 11 patients (36.7%) were able to achieve or maintain baseline major molecular response (MMR). 

Among patients who did not have a CCyR at baseline, the probabilities of obtaining CCyR, MMR, and deep molecular response (MR^4.5) were 13%, 11%, and 14%, respectively. Among patients who had a baseline CCyR, the probabilities of obtaining MMR and MR^4.5 were 40% and 20%, respectively.

Median event-free survival was 11.7 months. Event-free and progression-free survival estimates for 20 months were 63.3% and 80%, respectively.

The most frequent adverse events associated with bosutinib were anemia (23.3%), rash (23.3%), diarrhea (20%), edema (20%), neutropenia (16.7%), thrombocytopenia (16.7%), and fatigue (10%). Ten percent of patients discontinued therapy due to toxicity.

The authors noted that of the 15 patients who had previously suffered pleural effusion with dasatinib, none experienced this adverse event on bosutinib; and of the 10 patients who had previously suffered vascular events with nilotinib, none experienced these adverse events on bosutinib.

“Our results show that bosutinib is a valid option for patients who are not candidates to, or are waiting for, allogeneic transplantation. In addition, the lack of vascular events makes bosutinib a good option to patients in which ponatinib is considered, but have cardiovascular risk factors,” the authors concluded.