Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients

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 of...

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Published in:Annals of hematology 2019-02, Vol.98 (2), p.321-330
Main Authors: García-Gutiérrez, Valentín, Milojkovic, Dragana, Hernandez-Boluda, Juan Carlos, Claudiani, Simone, Martin Mateos, María Luisa, Casado-Montero, Luis Felipe, González, Gloria, Jimenez-Velasco, Antonio, Boque, Concepcion, Martinez-Trillos, Alejandra, Vázquez, Isabel Mata, Payer, Ángel Ramírez, Senín, Alicia, Amustio Díez, Elena, García, Abelardo Bárez, Carrascosa, Guiomar Bautista, Ortí, Guillermo, Ruiz, Beatriz Cuevas, Fernández, Maria Ángeles, del Carmen García Garay, María, Giraldo, Pilar, Guinea, Jose María, De Las Heras Rodríguez, Natalia, Hernán, Nuria, Pérez, Ana Iglesias, Piris-Villaespesa, Miguel, Lorenzo, Jose Luis López, Martí-Tutusaus, Josep Maria Martí, Vallansot, Rolando Omar, Ortega Rivas, Fernando, Puerta, Jose Manuel, Ramirez, Maria Jose, Romero, Esperanza, Romo, Andres, Rosell, Ana, Saavedra, Silvanna Saavedra, Sebrango, Ana, Tallon, José, Valencia, Sandra, Portero, Angeles, Steegmann, Juan Luis
Format: Article
Language:English
Subjects:
Hematology
Inhibitor drugs
Leukemia
Medicine
Medicine & Public Health
Oncology
Original Article
Targeted cancer therapy
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Summary: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.
ISSN:0939-5555
1432-0584
DOI:10.1007/s00277-018-3507-2