Treatment of Philadelphia-Positive Chronic Myeloid Leukemia with Imatinib: Importance of a Stable Molecular Response

• Published in: Clinical cancer research 2009-02, Vol.15 (3), p.1059-1063
• Main Authors: PALANDRI, Francesca, LACOBUCCI, Ilaria, VARALDO, Riccardo, ABRUZZESE, Elisabetta, MARTINO, Bruno, LUCIANO, Luigiana, PANE, Fabrizio, SAGLIO, Giuseppe, MARTINELLI, Giovanni, BACCARANI, Michele, ROSTI, Gianantonio, SOVERINI, Simona, CASTAGNETTI, Fausto, POERIO, Angela, TESTONI, Nicoletta, ALIMENA, Giuliana, BRECCIA, Massimo, REGE-CAMBRIN, Giovanna, TIRIBELLI, Mario
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Benzamides; Biological and medical sciences; chronic myeloid leukemia; Disease-Free Survival; Female; Fusion Proteins, bcr-abl - analysis; Hematologic and hematopoietic diseases; Humans; imatinib; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; long-term results; Male; Medical sciences; Middle Aged; molecular response; Pharmacology. Drug treatments; Piperazines; Prognosis; Pyrimidines; Time Factors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-1195

Purpose: The achievement of a major molecular response (MMolR) at 12 months is a surrogate marker of progression-free survival in chronic myeloid leukemia patients treated with imatinib. Experimental Design: We evaluated the prognostic value of the long-term evolution of the molecular response based on a retrospective analysis of 130 late chronic phase chronic myeloid leukemia patients who achieved a complete cytogenetic response (CCgR) with 400 mg/d imatinib and have now a median follow-up of 72 months (range, 48-77). Results: In 71 (55%) patients, molecular response was consistently major (stable MMolR); in 19 (15%) patients, molecular response was occasionally less than major (unstable MMolR); in 40 (30%) patients, MMolR was never achieved (never MMolR) during all the course of CCgR. Patients with stable MMolR had a longer CCgR duration and a significantly better progression-free survival compared with patients with absent or unstable MMolR. The achievement of a MMolR, if maintained continuously, conferred a marked long-term stability to the CCgR: patients with a stable MMolR have a significantly lower risk of losing the CCgR than patients with unstable and never MMolR (4% versus 21%, P = 0.03, and 4% versus 33%, P < 0.0001, respectively). Finally, if a MMolR is not maintained consistently, the risk of losing the CCgR is higher but not significantly than if it is never achieved (33% versus 21%, P = 0.5). Conclusions: These data confirm that achieving a MMolR is prognostically important but point out that the prognostic value of achieving a MMolR is greater if the response is confirmed and stable.