Iurlo Alessandra, Breccia Massimo, Stagno Fabio, Abruzzese Elisabetta, Pane Fabrizio, Attolico Immacolata, Sportoletti Paolo, Cerrano Marco, Galimberti Sara, Scappini Barbara, Miglino Maurizio, Siragusa Sergio, Capodanno Isabella, Valsecchi Diletta, Nardozza Aurelio Pio, Misto Alessandra, Coco Paola, Saglio Giuseppe, Rosti Gianantonio
Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Hematology, Department of Translational and Precision Medicine, Policlinico Umberto I, Sapienza University, Rome, Italy.
Hematol Oncol. 2025 Sep;43(5):e70126. doi: 10.1002/hon.70126.
Treatment-free remission (TFR) in chronic myeloid leukemia (CML) can be considered for patients in sustained deep molecular response (DMR) who can discontinue tyrosine kinase inhibitors (TKIs) while maintaining responses. Studies suggest that TKI de-escalation before TFR is feasible. This phase II study evaluated nilotinib de-escalation outcomes in adults with CML in chronic phase (CP) treated with first-line nilotinib for ≥ 3 years and in sustained DMR for ≥ 1 year. The study had four phases: screening, de-escalation (week 0-48), TFR (week 48-144) and follow-up. During de-escalation, patients received nilotinib 300 mg once daily, and those with sustained DMR entered TFR and discontinued nilotinib. Patients with major molecular response (MMR) but without sustained DMR continued nilotinib. At the data cut-off, 107 patients entered, and 98 (91.6%) completed de-escalation. TFR was entered by 90 patients (84.1%) with sustained DMR. At 96 weeks, 71/107 patients (66.4%) were in full TFR; 64/90 patients (71.1%) who entered TFR remained in ≥ MMR, and the median time-to-loss of MMR was not reached. During TFR, adverse events occurred in 64 patients (71.1%), including one serious event (pneumonia). Our data suggest that the de-escalation of nilotinib before a TFR attempt in CML-CP patients with sustained DMR can be a successful dose optimization strategy.
对于处于持续深度分子反应（DMR）且能够在维持反应的同时停用酪氨酸激酶抑制剂（TKIs）的慢性髓性白血病（CML）患者，可以考虑无治疗缓解（TFR）。研究表明，在实现TFR之前降低TKI剂量是可行的。这项II期研究评估了一线使用尼罗替尼治疗≥3年且处于持续DMR≥1年的慢性期（CP）CML成年患者中尼罗替尼剂量降低的结果。该研究有四个阶段：筛查、剂量降低（第0 - 48周）、TFR（第48 - 144周）和随访。在剂量降低阶段，患者每日服用一次300mg尼罗替尼，那些维持DMR的患者进入TFR阶段并停用尼罗替尼。达到主要分子反应（MMR）但未维持DMR的患者继续服用尼罗替尼。在数据截止时，107例患者入组，98例（91.6%）完成剂量降低阶段。90例（84.1%）维持DMR的患者进入TFR阶段。在第96周时，107例患者中有71例（66.4%）实现完全TFR；进入TFR阶段的90例患者中有64例（71.1%）维持在≥MMR状态，MMR丧失的中位时间未达到。在TFR阶段，64例患者（71.1%）发生不良事件，包括1例严重事件（肺炎）。我们的数据表明，对于具有持续DMR的CML - CP患者，在尝试实现TFR之前降低尼罗替尼剂量可能是一种成功的剂量优化策略。
