在停止伊马替尼治疗后疾病持续不可检测的慢性期慢性髓性白血病患者中，主要分子学反应缺失可作为重新开始酪氨酸激酶抑制剂治疗的触发因素。

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.

机构信息

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.

出版信息

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

DOI:10.1200/JCO.2012.48.5797

PMID:24323036

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.

摘要

目的

在伊马替尼停药后，有超过一半的慢性期慢性髓性白血病（CP-CML）患者达到完全分子学缓解（CMR）后会发生分子学复发。我们研究了主要分子学缓解（MMR）的丧失作为恢复治疗的标准。

方法

一项多中心观察性研究（A-STIM [根据停止伊马替尼]）评估了 80 例 CP-CML 患者在达到 CMR 后停止伊马替尼治疗的 MMR 持续情况。

结果

从伊马替尼开始到停药的中位时间为 79 个月（范围，30 至 145 个月）；伊马替尼停药前 CMR 的中位持续时间为 41 个月（范围，24 至 96 个月）；停药后的中位随访时间为 31 个月（范围，8 至 92 个月）。29 例患者（36%）在停药后中位 4 个月时失去 MMR（范围，2 至 17 个月）。12 个月时 MMR 丧失的累积发生率估计为 35%（95%CI，25%至 46%），24 个月时为 36%（95%CI，26%至 47%），而 CMR 丧失的概率更高。伊马替尼停药后，31%的患者 BCR-ABL 转录本水平低于 MMR 阈值（≥连续两个阳性值）波动。12 个月和 24 个月时无治疗缓解的估计率为 64%（95%CI，54%至 75%），36 个月时为 61%（95%CI，51%至 73%）。再次治疗患者的中位至第二次 MMR 的时间估计为 7.3 个月。