An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Autor: Steegmann JL; Hematology Service, Advanced Therapies in Oncohematology, IIS-IP, Hospital de la Princesa, Madrid, Spain. jlsteegmann.hlpr@salud.madrid.org., Colomer D; Unitat d' Hematopatologia, Hospital Clinic, Barcelona, Spain., Gómez-Casares MT; Laboratorio de Hematología, Biología Molecular, Hospital Universitario de Gran Canaria Dr.Negrín, Las Palmas, Spain., García-Gutiérrez V; Servicio de Hematología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain., Ortí G; Hematology Department, Hospital Universitari Vall d´Hebron, VHIO, Barcelona, Spain., Ramírez-Payer A; Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain., Olavarria E; Hematology Department, Imperial College Healthcare NHS Trust, London, UK., Vall-Llovera F; Servicio de Hematología, Hospital Universitari Mútua Terrassa, Terrassa, Spain., Giraldo P; Instituto Investigación Sanitaria Aragón (IIS Aragon), CIBERER, Zaragoza, Spain., Conde E; Hematologia, Universidad de Cantabria, Santander, Spain., Vallansot R; Servei d´Hematologia, ICO-Tarragona, Hospital Universitari Joan XXIII, Tarragona, Spain., López-Lorenzo JL; Hematologia, Clínica de la Concepción, Madrid, Spain., Palomera L; Hospital Clínico Universitario Lozano Blesa, Instituto Investigación (ISS) Aragón, Zaragoza, Spain., Álvarez-Larrán A; Hematology Department, Hospital del Mar-IMIM, Barcelona, Spain., Conesa V; Hematología, Departament de Salut d'Elx, Hospital General, Elche, Spain., Bautista G; Hematología, Hospital Puerta de Hierro, Madrid, Spain., Casas L; Statistics Department, Dynamic Solutions, SL, Barcelona, Spain., Giles F; Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, USA., Hochhaus A; Klinik für Innere Medizin II. Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany., Casado-Montero LF; Servicio de Hematología y Hemoterapia, Hospital Virgen de la Salud, Toledo, Spain.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2017 Oct; Vol. 143 (10), pp. 2059-2066. Date of Electronic Publication: 2017 May 27.
DOI: 10.1007/s00432-017-2445-z
Abstrakt: Purpose: This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter.
Methods: This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter).
Results: The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months.
Conclusions: The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.
Databáze: MEDLINE
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