PS1176 PRIMARY RESULTS OF THE PHASE 4 BYOND STUDY OF BOSUTINIB FOR PRETREATED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA
Authors: Hochhaus A. , Gambacorti‐Passerini C. , Abboud C. , Gjertsen B.T. , Brümmendorf T.H. , Smith B.D. , Giraldo‐Castellano P. , Strömberg U. , Saussele S. , Bardy‐Bouxin N. , Viqueira A. , Leip E. , Leone J. , Rosti G. , Watts J. , Giles F. ,   BYOND Study Investigators
Published: June 2019

Background:The tyrosine kinase inhibitor (TKI) bosutinib is approved for patients with Philadelphia chromosome (Ph)+ chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and newly diagnosed patients in chronic phase (CP).Aims:The ongoing phase 4 BYOND study (NCT02228382) is further evaluating the efficacy and safety of bosutinib for CML resistant/intolerant to prior TKIs.Methods:Patients with CML and resistance/intolerance to previous TKI therapy were administered bosutinib at a starting dose 500 mg/d. Primary endpoint (not powered) in Ph+ CP CML cohorts is cumulative confirmed major cytogenetic response (MCyR) by 1 y.Results:Of 163 patients who received bosutinib, 156 had Ph+ CP CML (46, 61 and 49 after 1, 2 and 3 prior TKIs, respectively); 4 patients with accelerated phase CML and 3 with Ph–/BCR‐ABL+ CML were analyzed for efficacy separately. Across Ph+ CP CML cohorts, 51.9% of patients were male, and median age was 61 y. 53.2% of patients were resistant to ≥1 prior TKI and 46.8% intolerant to all. As of 1 y after last enrolled patient (median follow‐up 30.4 mo), 56.4% remained on bosutinib. Median treatment duration was 23.7 mo, and median dose intensity was 313 mg/d. Of 144 evaluable patients with a valid baseline assessment, cumulative confirmed MCyR by 1 y was 71.5% (95% confidence interval [CI] 63.4–78.7). Cumulative complete cytogenetic response rate anytime on treatment was 81.3% (95% CI 73.9–87.3). A substantial proportion of patients attained or maintained molecular responses (MRs) across lines of therapy (Table). Of 76 TKI‐resistant and 73 TKI‐intolerant patients evaluable for MR, respectively, cumulative major MR (MMR) rates were 61.8% (95% CI 50.0–72.8) and 82.2% (95% CI 71.5–90.2), MR4 rates were 46.1% (95% CI 34.5–57.9) and 68.5% (95% CI 56.6–78.9) and MR4.5 rates were 36.8% (95% CI 26.1–48.7) and 56.2% (95% CI 44.1–67.8). Among 48 TKI‐resistant and 31 TKI‐intolerant patients without baseline MMR, respectively, cumulative MMR rates were 45.8% (95% CI 31.4–60.8) and 80.6% (95% CI 62.5–92.5), MR4 rates were 22.9% (95% CI 12.0–37.3) and 61.3% (95% CI 42.2–78.2) and MR4.5 rates were 16.7% (95% CI 7.5–30.2) and 51.6% (95% CI 33.1–69.8). 10 deaths occurred (5 on treatment; 0 due to bosutinib toxicity); 1‐y overall survival rate was 98.0% (95% CI 94.0–99.4). No patient progressed to accelerated/blast phase on treatment. 25.0% discontinued bosutinib due to adverse events (AEs) and 5.1% due to insufficient response. Individual treatment‐emergent AEs (TEAEs) reported in >20% of patients across all cohorts (N = 163) were diarrhea (87.7%), nausea (39.9%), vomiting (32.5%), abdominal pain (28.2%), headache (27.6%), increased alanine aminotransferase (ALT; 25.8%), fatigue (23.9%), upper abdominal pain (22.1%), dyspnea (21.5%) and asthenia (20.2%). Grade 3/4 TEAEs in >10% of patients were diarrhea (16.0%) and increased ALT (14.1%). No individual TEAE led to discontinuation in >5% of patients. In all, 28.8% of patients had liver TEAEs (consisting of a cluster of predefined AEs), 14.7% had grade 3/4 liver TEAEs and 5.5% had liver TEAEs leading to bosutinib discontinuation.Summary/Conclusion:Most pretreated patients with Ph+ CP CML had confirmed MCyR by 1 y with bosutinib. MMRs and deep MRs were seen in TKI‐resistant and TKI‐intolerant patients and in all therapy lines, with >45% of TKI‐resistant and >80% of TKI‐intolerant patients achieving MMR or deeper MR with bosutinib. Results further support bosutinib use for patients with Ph+ CP CML resistant/intolerant to prior TKIs.image