Bosutinib for Patients with Previously Treated Chronic Myeloid Leukemia: Results from the French Observational Boseval Study

Background: Bosutinib (BOS) is approved in France for the treatment of newly diagnosed Philadelphia chromosome–positive (Ph+) chronic phase chronic myeloid leukemia (CML), and for patients (pts) with Ph+ CML previously treated with ≥1 tyrosine kinase inhibitor (TKI) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

Aims: This study aimed to characterize the safety and effectiveness of BOS in pts with previously treated CML receiving treatment in a real-world clinical setting in France.

Methods: BOSEVAL is a non-interventional, observational, prospective study conducted at 23 centers in Metropolitan France. Eligible pts, aged ≥18 yr, had a diagnosis of Ph+ and/or BCR::ABL1+ CML and were resistant/intolerant to prior treatment with ≥1 TKI. Primary outcomes measures were treatment-related adverse events (TRAEs) and permanent BOS discontinuation due to TRAEs, as determined by the investigator.

Results: This study included 142 pts who commenced BOS treatment between Oct 22, 2015, and Dec 19, 2019, with a follow-up period of 3 yr from BOS initiation. Among the 139 pts evaluable for effectiveness, the median age at BOS initiation was 65.0 (range, 23.0−88.0) yr, 56.1% were male; 46.0%, 30.2% and 23.7% of pts received BOS as 2^nd, 3^rd, and ≥4^th line treatment, respectively. Median time from CML diagnosis to the initiation of BOS treatment was 3.9 (range, 0.2−29.2) yr. In all, 64.7% of pts switched to BOS due to intolerance to their last TKI therapy; most common (≥20%) TKI therapies prior to BOS initiation were imatinib (46.8%) and dasatinib (33.1%).

At study completion (median follow-up, 3.1 yr), 55.6% of pts were still receiving BOS; median duration of treatment was 2.8 (range, 0−3.4) yr. Median dose at treatment initiation was 200 (range, 100−500) mg/day, and the average dose during treatment was 300 (range, 57−500) mg/day. Dose escalations were reported in 76.1% of pts. Dose reductions and dose interruptions occurred in 50.0% and 43.7% of pts, respectively. Most common primary reasons for permanent BOS discontinuation were intolerance (27.5%) and loss of response/suboptimal response (11.3%).

Adverse events (AEs) were reported in 99.3% of pts; 60.6% of patients experienced at least one serious AE and 88.0% of patients experienced TRAEs. Most common (≥10%) any grade TRAEs were diarrhea (53.5%), hepatocellular injury (14.8%), nausea (14.1%) and abdominal pain (10.6%). TRAEs led to permanent treatment discontinuation in 26.8% of pts; the most common (≥2%) were diarrhea, pleural effusion, hepatocellular injury, increased aspartate/alanine aminotransferase and vomiting in 7.7%, 4.9%, 4.9%, 2.8% and 2.1% of patients, respectively. BOS cross-intolerance was reported in 7 pts; cross-intolerance due to recurrence of pleural effusions was reported in 3 dasatinib-intolerant pts and 1 dasatinib and imatinib-intolerant pt, cross-intolerance due to cardiac failure, pain or diarrhea was reported in 3 imatinib-intolerant pts.

Among the 139 pts, evaluable for effectiveness, 70.5% attained or maintained molecular responses at any time on treatment (MMR, 15.1%; MR4, 10.1%; MR4.5, 15.8%; MR5, 29.5%). Among responders, the Kaplan-Meier probability of maintaining a molecular response at 3 yr was 81% (95% CI, 72–88). On-treatment transformations to accelerated and blast phase occurred in 3 (2.2%) pts and 1 (0.7%) pt, respectively. The Kaplan-Meier estimated progression-free and overall survival rates at 3 yr were 93% (95% CI, 87−96) and 95% (95% CI, 89−97), respectively. During the study, 7 deaths occurred; 2 were considered related to CML and 1 was TRAE (pneumonia) per investigators.

Conclusions: This real-world analysis characterized the safety and effectiveness of BOS in previously treated pts with CML in France.