Hughes Timothy P, Yong Agnes Sm, Ross David M
South Australian Health and Medical Research Institute, Adelaide, Australia.
South Australian Health & Medical Research Institute, Australia.
Blood. 2025 Jan 6. doi: 10.1182/blood.2024026310.
One of the most remarkable achievements of the TKI era has been the capacity to induce deep molecular remissions that are sustainable off therapy in chronic myeloid leukemia (CML) patients - treatment-free remission (TFR). TFR was first described in a handful of patients within 3-4 years of imatinib approval. In 2004 TFR was tested in a small French pilot study, followed soon after by the French STIM and Australasian TWISTER studies. These early trials demonstrated that TFR was achievable, but also showed that rapid relapse was equally likely. Perhaps the most critical observation was that relapsing patients could be rapidly and safely returned to deep molecular remission after restarting therapy, minimising the risk associated with TFR attempts. Consensus criteria for TFR eligibility were established soon after those studies were reported. Over the past decade TFR criteria have been broadened, key predictive markers of success identified, and overall safety of TFR in the wider clinical community confirmed. Despite this progress, TFR is still only achieved in a fraction of CML patients globally. Over the next decade the focus will be making TFR the mainstream pathway for as many patients as possible as well as scaling back the duration of therapy required. More potent, better targeted TKIs, and immune modulation will likely have a significant impact. Predictive assays should enable most patients who attempt TFR to do so with a high probability of success. Ultimately TFR should be seen as the first step on an ambitious pathway towards cure for CML patients.
酪氨酸激酶抑制剂（TKI）时代最显著的成就之一，是能够在慢性髓性白血病（CML）患者中诱导出深度分子缓解，且在停止治疗后仍可持续——即无治疗缓解（TFR）。TFR最早在伊马替尼获批后的3 - 4年内，在少数患者中被描述。2004年，TFR在一项小型法国试点研究中进行了测试，随后不久法国的STIM研究和澳大利亚的TWISTER研究也相继开展。这些早期试验表明TFR是可以实现的，但也表明快速复发同样有可能发生。或许最关键的观察结果是，复发患者在重新开始治疗后能够迅速且安全地恢复到深度分子缓解状态，从而将与尝试TFR相关的风险降至最低。在这些研究报告后不久，就确立了TFR资格的共识标准。在过去十年中，TFR标准得到了拓宽，成功的关键预测标志物得以确定，并且TFR在更广泛临床群体中的总体安全性也得到了证实。尽管取得了这一进展，但在全球范围内，仍只有一小部分CML患者能够实现TFR。在接下来的十年里，重点将是使TFR成为尽可能多患者的主流治疗途径，并缩短所需的治疗持续时间。更有效、靶向性更强的TKI以及免疫调节可能会产生重大影响。预测性检测应能使大多数尝试TFR的患者有很高的成功概率。最终，TFR应被视为CML患者通往治愈这一宏伟道路上的第一步。
