Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature.

摘要: // Ivan Alvarez-Twose 1, 5 , Almudena Matito Jose Mario Morgado Laura Sanchez-Munoz Maria Jara-Acevedo 2, Andres Garcia-Montero Andrea Mayado Carolina Caldas Cristina Teodosio 3 Javier Ignacio Munoz-Gonzalez Manuela Mollejo 4, Luis Escribano and Alberto Orfao 1 Instituto de Estudios Mastocitosis Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain 2 Centro Investigacion Cancer/IBMCC (USAL/CSIC) IBSAL, Departamento Medicina Servicio General Citometria, University of Salamanca, Department Immunology, Erasmus Medical Center, Rotterdam, The Netherlands 4 Pathology, la Salud, Spanish Network on Mastocytosis (REMA), Toledo Correspondence to: Alvarez-Twose, email: ivana@sescam.jccm.es Keywords: mast cell, mastocytosis, well-differentiated systemic imatinib, KIT Received: March 01, 2016      Accepted: May 29, Published: July 19, 2016 ABSTRACT Resistance to imatinib has been recurrently reported in mastocytosis (SM) carrying exon 17 mutations. We evaluated the efficacy safety therapy 10 adult SM patients lacking mutations, 9 which fulfilled criteria for (WDSM). World Health Organization 2008 disease categories among WDSM were cell (MC) leukemia ( n = 3), indolent 3) cutaneous 3); remainder case had associated with a clonal haematological non-MC disease. Patients given 12 months –400 or 300 mg daily depending presence vs. absence > 30% bone marrow (BM) MCs and/or signs advanced disease–. Absence mutations was confirmed highly-purified BM by peptide nucleic acid-mediated PCR, while involving other exons investigated direct sequencing purified MC DNA. Complete response (CR) defined as resolution infiltration, skin lesions, organomegalies MC-mediator release-associated symptoms, plus normalization serum tryptase. Criteria partial (PR) included ≥ 50% reduction infiltration improvement lesions organomegalies. Treatment well-tolerated an overall rate 50%, including early sustained CR four patients, three whom extracellular PR one case. This later patient all non-responders 5) showed wild-type . These results together previous data from literature support relevance mutational status selecting who are candidates therapy.