title: Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease.
abstract: OBJECTIVE
  More than half of patients with chronic-phase chronic myelogenous leukemia (CP-CML) in complete molecular response (CMR) experience molecular relapse after imatinib discontinuation. We investigated loss of major molecular response (MMR) as a criterion for resuming therapy.
  
  
  METHODS
  A multicenter observational study (A-STIM [According to Stop Imatinib]) evaluating MMR persistence was conducted in 80 patients with CP-CML who had stopped imatinib after prolonged CMR.
  
  
  RESULTS
  Median time from imatinib initiation to discontinuation was 79 months (range, 30 to 145 months);median duration of CMR before imatinib discontinuation was 41 months (range, 24 to 96 months); median follow-up after discontinuation was 31 months (range, 8 to 92 months). Twenty-nine patients (36%) lost MMR after a median of 4 months off therapy (range, 2 to 17 months). Cumulative incidence of MMR loss was estimated as 35% (95% CI, 25% to 46%) at 12 months and 36% (95% CI, 26% to 47%) at 24 months, whereas probability of losing CMR was higher. Fluctuation of BCR-ABL transcript levels below the MMR threshold (≥ two consecutive positive values) was observed in 31% of patients after imatinib discontinuation. Treatment-free remission was estimated as 64% (95% CI, 54% to 75%) at 12 and 24 months and 61% (95% CI, 51% to 73%) at 36 months. Median to time to second CMR was estimated as 7.3 months in re-treated patients.
  
  
  CONCLUSIONS
  Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR.
authors: Philippe Rousselot, Hôpital Mignot, Université Versailles Saint-Quentin-en-Yvelines, Versailles; Aude Charbonnier, Institut Paoli Calmette, Marseille; Pascale Cony-Makhoul, Hôpital d'Annecy, Pringy; Philippe Agape, Hôpital Felix Guyon-Centre Hospitalier Universitaire en France (CHU) de la Réunion, La Réunion; Franck E. Nicolini, Centre Hospitalier Lyon Sud, Pierre-Bénite; Bruno Varet, Hôpital Necker, Assistance Publique-Hopitaux de Paris (AP-HP) et Université Paris Descartes; Delphine Réa and Jean Michel Cayuela, Hôpital Saint-Louis, AP-HP, Paris; Martine Gardembas, CHU d'Angers, Angers; Gabriel Etienne and Josy Reiffers, Institut Bergonié; François-Xavier Mahon, Hôpital Haut-Levèque et Université Bordeaux Ségalen, Bordeaux; Lydia Roy, Joëlle Guilhot, and François Guilhot, Institut National de la Santé et de la Recherche Médicale (INSERM) Centres d'Investigation Clinique CHU de Poitiers, Poitiers; Martine Escoffre-Barbe, Centre Hospitalier Pontchaillou, Rennes; Agnès Guerci-Bresler, CHU Brabois Vandoeuvre, Nancy; Michel Tulliez, Hôpital Henri Mondor, AP-HP, Créteil; Stéphane Prost, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses; Marc Spentchian, Hôpital Mignot, Le Chesnay; and Jean Claude Chomel and Ali Turhan, INSERM U935, Université Poitiers et Paris Sud, Le Kremlin Bicêtre, France.
authors: Philippe
authors: P
authors: Rousselot
authors: Aude
authors: A
authors: Charbonnier
authors: Pascale
authors: P
authors: Cony-Makhoul
authors: Philippe
authors: P
authors: Agape
authors: Franck E
authors: FE
authors: Nicolini
authors: Bruno
authors: B
authors: Varet
authors: Martine
authors: M
authors: Gardembas
authors: Gabriel
authors: G
authors: Etienne
authors: Delphine
authors: D
authors: Réa
authors: Lydia
authors: L
authors: Roy
authors: Martine
authors: M
authors: Escoffre-Barbe
authors: Agnès
authors: A
authors: Guerci-Bresler
authors: Michel
authors: M
authors: Tulliez
authors: Stéphane
authors: S
authors: Prost
authors: Marc
authors: M
authors: Spentchian
authors: Jean Michel
authors: JM
authors: Cayuela
authors: Josy
authors: J
authors: Reiffers
authors: Jean Claude
authors: JC
authors: Chomel
authors: Ali
authors: A
authors: Turhan
authors: Joëlle
authors: J
authors: Guilhot
authors: François
authors: F
authors: Guilhot
authors: François-Xavier
authors: FX
authors: Mahon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl