Published in:
01-02-2019 | Original Article
Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients
Authors:
Valentín García-Gutiérrez, Dragana Milojkovic, Juan Carlos Hernandez-Boluda, Simone Claudiani, María Luisa Martin Mateos, Luis Felipe Casado-Montero, Gloria González, Antonio Jimenez-Velasco, Concepcion Boque, Alejandra Martinez-Trillos, Isabel Mata Vázquez, Ángel Ramírez Payer, Alicia Senín, Elena Amustio Díez, Abelardo Bárez García, Guiomar Bautista Carrascosa, Guillermo Ortí, Beatriz Cuevas Ruiz, Maria Ángeles Fernández, María del Carmen García Garay, Pilar Giraldo, Jose María Guinea, Natalia De Las Heras Rodríguez, Nuria Hernán, Ana Iglesias Pérez, Miguel Piris-Villaespesa, Jose Luis López Lorenzo, Josep Maria Martí Martí-Tutusaus, Rolando Omar Vallansot, Fernando Ortega Rivas, Jose Manuel Puerta, Maria Jose Ramirez, Esperanza Romero, Andres Romo, Ana Rosell, Silvanna Saavedra Saavedra, Ana Sebrango, José Tallon, Sandra Valencia, Angeles Portero, Juan Luis Steegmann, On behalf of Grupo Español de Leucemia Mieloide Crónica (GELMC)
Published in:
Annals of Hematology
|
Issue 2/2019
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Abstract
Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9–163) months, and median duration on bosutinib was 9 months (1–30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients’ cohort. Pleural effusions and diarrhea were the most frequent grade II–IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.