Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study
Andreas Hochhaus, Carlo Gambacorti‐Passerini, Camille N. Abboud, Bjørn Tore Gjertsen, Tim H. Brümmendorf, B. Douglas Smith, Thomas Ernst, Pilar Giraldo-Castellano, Ulla Olsson‐Strömberg, Susanne Saußele, Nathalie Bardy‐Bouxin, Andrea Viqueira, Eric Leip, T. Alexander Russell-Smith, Jocelyn M Leone, Gianantonio Rosti, Justin M. Watts, Francis J. Giles, on behalf of the BYOND Study Investigators, Elisabetta Abruzzese, L Akard, Alberto Bosi, F. Cervantes, Aude Charbonnier, Francesco Di Raimondo, Gabriel Etienne, V. Garcia Gutierrez, Agnès-Paule Guerci-Bresler, Henrik Hjorth‐Hansen, Jean Michel Karsenti, Kevin R. Kelly, P. Le Coutre, Carmen Martínez Chamorro, Vivian G. Oehler, G. Orti Pascual, Andreas Petzer, Ester Pungolino, Giovanna Rege‐Cambrin, Françoise Rigal‐Huguet, Gail J. Roboz, P. Rousselot, Fermín Sánchez‐Guijo, Guillermo Sanz Santillana, Philippe Schafhausen, C. Scheid, Stefan Schmidt, Giorgina Specchia, Juan Luis Steegmann, Leif Stenke
Abstract
Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.