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J Clin Oncol. 2014 Feb 10;32(5):424-30. doi: 10.1200/JCO.2012.48.5797. Epub 2013 Dec 9.

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.

Author information

1
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.

Abstract

PURPOSE:

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.

PATIENTS AND 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.

CONCLUSION:

Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR.

PMID:
24323036
DOI:
10.1200/JCO.2012.48.5797
[Indexed for MEDLINE]

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