title: Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?
abstract: In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival.
authors: Servicio Hematología y Hemoterapia, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors: Valentin
authors: V
authors: García-Gutiérrez
authors: Jose Manuel
authors: JM
authors: Puerta
authors: Begoña
authors: B
authors: Maestro
authors: Luis Felipe
authors: LF
authors: Casado Montero
authors: Alfonso
authors: A
authors: Muriel
authors: Jose Ramon
authors: JR
authors: Molina Hurtado
authors: Manuel
authors: M
authors: Perez-Encinas
authors: Maria Victoria
authors: MV
authors: Moreno Romero
authors: Pere Barba
authors: PB
authors: Suñol
authors: Ricardo
authors: R
authors: Sola Garcia
authors: Raquel
authors: R
authors: De Paz
authors: Maria Jose
authors: MJ
authors: Ramirez Sanchez
authors: Santiago
authors: S
authors: Osorio
authors: Maria Isabel
authors: MI
authors: Mata Vazquez
authors: Joaquin
authors: J
authors: Martinez López
authors: Jose Luis
authors: JL
authors: Sastre
authors: Maria de Los Angles
authors: Mde L
authors: Portero
authors: Guiomar
authors: G
authors: Bautista
authors: Maria Soledad
authors: MS
authors: Duran Nieto
authors: Pilar
authors: P
authors: Giraldo
authors: Margarita
authors: M
authors: Jimenez Jambrina
authors: Carmen
authors: C
authors: Burgaleta
authors: Joaquin
authors: J
authors: Ruiz Aredondo
authors: Maria Jesús
authors: MJ
authors: Peñarrubia
authors: Maria José
authors: MJ
authors: Requena
authors: María Del Carmen
authors: Mdel C
authors: Fernández Valle
authors: Carmen
authors: C
authors: Calle
authors: Antonio
authors: A
authors: Paz Coll
authors: Jose Ángel
authors: JÁ
authors: Hernández-Rivas
authors: Rafael
authors: R
authors: Franco Osorio
authors: Pilar
authors: P
authors: Cano
authors: David
authors: D
authors: Tallón Pérez
authors: Margarita
authors: M
authors: Fernández de la Mata
authors: Pilar López
authors: PL
authors: Garrido
authors: Juan Luis
authors: JL
authors: Steegmann
mesh_terms: D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D057915:Drug Substitution; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000097:blood*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015337:Multicenter Studies as Topic; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D057832:Watchful Waiting
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib