慢性期慢性髓系白血病(TKI 可中断)患者进展风险：TFR-PRO 研究的最终分析。
Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study.
发表日期：2023 Aug 30
作者：
Giovanni Paolo Maria Zambrotta, Franck E Nicolini, Sarit Assouline, Lambert Busque, Ester Pungolino, Elisabetta Abruzzese, Maria Cristina Miggiano, Chiara Elena, Alberto Alvarez-Larran, Ana Triguero, Alessandra Iurlo, Cristina Bucelli, Marco Cerrano, Isabella Capodanno, Francesca Lunghi, Philipp le Coutre, Sara Galimberti, Giovanni Caocci, Margherita Maffioli, Fabio Stagno, Susanne Saussele, Rocco Piazza, Brian J Druker, Carmen Fava, Veronica Guglielmana, Federica Colombo, Laura Antolini, Carlo Gambacorti-Passerini
来源：
AMERICAN JOURNAL OF HEMATOLOGY
摘要：
慢性期慢性髓系白血病（CP-CML）患者在治疗停药后加速/爆发期（AP/BP）的疾病进展，尚未在临床试验中有系统性报道。然而，最近有几个这样的病例的报道引起了关注。为了估计合适停药患者中AP/BP的风险，我们进行了名为TFR-PRO的回顾前瞻性队列研究：870例合乎停药条件的CP-CML患者形成了停药队列（505例患者）和参照队列（365例患者）。主要目标是停药与进展的时间调整率(TAR)。次要终点分析包括分子复发率，即主要分子反应(MMR)的丧失率。在平均随访时间为5.5年，共有5188.2人年的情况下，停药队列未发生任何事件。在停药结束后的55个月，当该患者属于参照队列时，发生了一次进展事件。总体组中进展的TAR为0.019/100人年（95％ CI [0.003-0.138]）。停药队列中的TAR为0.0（95％ CI [0-0.163]），而参照队列中为0.030（95％ CI [0.004-0.215]）。这些差异在统计上没有显著性。停药后，172/505（34.1%）患者发生分子复发事件，而在参照队列中，64/365（17.5%）患者发生了分子复发(p < .0001) 。在接受一线、二线或三线治疗的停药患者中观察到类似的率。合适停药患者中慢性骨髓性白血病的进展是罕见的，并与停药无关。对于试图停药的患者担心疾病进展的风险应该消除。© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003-0.138]) in the overall group; 0.0 (95% CI [0-0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004-0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p < .0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated.© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.