Smith, B. Douglas, Brümmendorf, Tim H., Roboz, Gail J., Gambacorti-Passerini, Carlo, Charbonnier, Aude, Viqueira, Andrea, Leip, Eric, Purcell, Simon, Goldman, Erinn Hoag, Giles, Francis, Ernst, Thomas, Hochhaus, Andreas, and Rosti, Gianantonio
The BYOND study evaluated the efficacy and safety of bosutinib 500 mg once daily in patients with chronic myeloid leukemia (CML) resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). These post-hoc analyses assessed the efficacy and safety of bosutinib by resistance or intolerance to prior TKIs (imatinib-resistant vs dasatinib/nilotinib-resistant vs TKI-intolerant), and cross-intolerance between bosutinib and prior TKIs (imatinib, dasatinib, nilotinib), in patients with Philadelphia chromosome–positive chronic phase CML. Data are reported after ≥3 years' follow-up. Of 156 patients with Philadelphia chromosome–positive chronic phase CML, 53 were imatinib-resistant, 29 dasatinib/nilotinib-resistant, and 74 intolerant to all prior TKIs; cumulative complete cytogenetic response rates at any time were 83.7%, 61.5%, and 86.8%, and cumulative major molecular response rates at any time were 72.9%, 40.7%, and 82.4%, respectively. Of 141, 95, and 79 patients who received prior imatinib, dasatinib, and nilotinib, 64 (45.4%), 71 (74.7%), and 60 (75.9%) discontinued the respective TKI due to intolerance; of these, 2 (3.1%), 5 (7.0%), and 0 had cross-intolerance with bosutinib. The response rates observed in TKI-resistant and TKI-intolerant patients, and low cross-intolerance between bosutinib and prior TKIs, further support bosutinib use for patients with Philadelphia chromosome–positive chronic phase CML resistant/intolerant to prior TKIs. ClinicalTrials.gov: NCT02228382 • Bosutinib was assessed in Ph+ CP CML patients resistant or intolerant to prior TKIs. • Response rates were high in imatinib-resistant and TKI-intolerant patients. • Rates were lower but responses durable in dasatinib/nilotinib-resistant patients. • Cross-intolerance between bosutinib and prior TKIs was low. • Bosutinib is a viable option after resistance or intolerance to prior TKIs. [ABSTRACT FROM AUTHOR]