Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program.

Abstract

The role of bosutinib as rescue treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients after failing three previous tyrosine kinase inhibitors (TKIs) is currently unknown. We report here the largest series (to our knowledge) of patients treated with bosutinib in fourth-line, after retrospectively reviewing 30 patients in chronic phase, and pretreated with imatinib, nilotinib, and dasatinib. With a median follow up of 11.1 months, the probability to either maintain or improve their CCyR response was 56.6% (17/30) and 11 patients (36.7%) achieved or maintained their baseline MMR. In patients not having baseline CCyR, the probabilities of obtaining CCyR, MMR, and MR4.5 were 13, 11, and 14%, respectively. The probabilities of obtaining MMR and deep molecular response MR4.5 in patients with baseline CCyR were 40.0% (6/15) and 20.0% (3/15). At 20 months, progression-free survival was 73%. Grade 3-4 hematological toxicities were more frequent in resistant than intolerant patients (45.4 vs. 0.0%). Nonhematological toxicities were also more frequent in resistant patients, being diarrhea the most conspicuous one. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKI's.

• Authors: Valentín García-Gutiérrez, Alejandra Martinez-Trillos, Jose Luis Lopez Lorenzo, Guiomar Bautista, Maria Luisa Martin Mateos, Alberto Alvarez-Larrán, Ana Iglesias Pérez, Andrés Romo Collado, Angeles Fernandez, Angeles Portero, Beatriz Cuevas, Concepción Ruiz, Esperanza Romero, Fernando Ortega, Isabel Mata, José Tallón, Maria Del Carmen García Garay, María José Ramirez Sánchez, Natalia de Las Heras, Pilar Giraldo, Sabela Bobillo, José María Guinea, Guillermo Deben, Sandra Valencia, Ana Sebrango, Concepción Boqué, Begoña Maestro, Juan Luis Steegmann
• Journal: American journal of hematology (Am J Hematol) Vol. 90 Issue 5 Pg. 429-33 (May 2015) ISSN: 1096-8652 [Electronic] United States
• PMID: 25683327 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Aniline Compounds
• Antineoplastic Agents
• Benzamides
• Nitriles
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Quinolines
• Thiazoles
• bosutinib
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• nilotinib
• Dasatinib

Topics

• Adult
• Aged
• Aniline Compounds (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Benzamides (therapeutic use)
• Compassionate Use Trials
• Dasatinib
• Drug Resistance, Neoplasm
• Female
• Humans
• Imatinib Mesylate
• Leukemia, Myeloid, Chronic-Phase (drug therapy, enzymology, mortality, pathology)
• Male
• Middle Aged
• Nitriles (therapeutic use)
• Piperazines (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Pyrimidines (therapeutic use)
• Quinolines (therapeutic use)
• Retrospective Studies
• Spain
• Survival Analysis
• Thiazoles (therapeutic use)