P719: EFFICACY AND SAFETY OF BOSUTINIB IN LATER-LINE PATIENTS WITH CHRONIC MYELOID LEUKEMIA: A SUB-ANALYSIS FROM THE PHASE 4 BYOND TRIAL

Abstract

Background: Bosutinib is approved for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) resistant or intolerant to prior therapy and newly diagnosed patients in chronic phase. The efficacy and safety of bosutinib in patients with CML resistant or intolerant to prior tyrosine kinase inhibitors (TKIs) was evaluated in the phase 4 BYOND trial (NCT02228382; Gambacorti-Passerini et al, Blood, 2021). Aims: The efficacy and safety of bosutinib in resistant and intolerant patients with CML treated with 2 (3L) and 3 (4L) prior TKIs was characterized. Methods: The BYOND trial included 163 patients with CML resistant or intolerant to prior TKIs. A sub-analysis of 48 patients treated with 2 (3L) and 3 (4L) prior TKIs, categorized by resistance or intolerance to the last received TKI, was performed. This sub-analysis is based on the final November 23, 2020 database lock. Results: There were 18 and 30 patients resistant or intolerant to the last received TKI who entered the study without complete cytogenetic response (CCyR) or major molecular response (MMR), respectively. Median (range) treatment duration was 10.6 months (1.6–48.5) vs 28.3 months (0.2–48.6) and median (range) dose intensity was 447.1 mg/d (131.3–520.4) vs 288.8 mg/d (79.7–500.0) for resistant vs intolerant patients. Prior TKIs included imatinib (88.9% vs 100.0%), dasatinib (88.9% vs 83.3%), and nilotinib (66.7% vs 63.3%) for resistant vs intolerant patients. Overall, 61.1% vs 66.7% of resistant vs intolerant patients discontinued bosutinib, mostly commonly due to adverse events (AEs) in 27.8% vs 16.7% patients; 16.7% vs 6.7% discontinued bosutinib due to insufficient clinical response. Rates of CCyR and MMR are shown in the Table. Among responders (resistant vs intolerant patients), median (range) time to CCyR was 5.1 months (2.8–8.8) vs 3.0 months (2.7–6.1); median (range) time to MMR was 5.8 months (2.8–9.4) vs 3.2 months (2.8–9.3). In resistant vs intolerant patients, any grade treatment-emergent AEs (TEAEs) were reported by 100.0% vs 96.7% patients; grade 3/4 TEAEs were reported by 72.2% vs 83.3% patients. Grade 3/4 TEAEs >10% in resistant patients were thrombocytopenia (22.2%) and neutropenia (11.1%), and in intolerant patients were increased alanine aminotransferase (26.7%), diarrhea (23.3%), pleural effusion (13.3%), and rash (13.3%). Image:Summary/Conclusion: This sub-analysis of resistant and intolerant patients without baseline CCyR or MMR shows bosutinib was active in heavily pretreated patients with resistance or intolerance to the last received TKI. Despite a difference between resistant and intolerant patients with CML, efficacy outcomes, though lower than the overall BYOND population, are encouraging, and safety was generally consistent with previous reports.