Breccia Massimo, Cucci Rosalba, Marsili Giovanni, Castagnetti Fausto, Galimberti Sara, Izzo Barbara, Sorà Federica, Soverini Simona, Messina Monica, Piciocchi Alfonso, Bonifacio Massimiliano, Cilloni Daniela, Iurlo Alessandra, Martinelli Giovanni, Rosti Gianantonio, Stagno Fabio, Fazi Paola, Vignetti Marco, Pane Fabrizio
Department of Translational and Precision Medicine, Università Sapienza, Rome, Italy.
GIMEMA Data Center, Rome, Italy.
Clin Lymphoma Myeloma Leuk. 2025 Jan;25(1):e34-e39. doi: 10.1016/j.clml.2024.08.009. Epub 2024 Sep 7.
In the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients.
Data were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring.
Out of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (P = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (P < .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (P < .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with <MR2, with dasatinib 66% versus 28% of patients with <MR2, and with nilotinib 75% versus 30% of patients with < MR2 (P < .001). At the same time point, achieving at least ≥MR3 is even more predictive of a DMR at any timepoint: 89% versus 38% of patients with <MR3 with imatinib (P < .001), 84% versus 40% of patients with <MR3 with dasatinib (P < .001), and 89% versus 49% of patients with <MR3 with nilotinib (P < .001). Of 908 patients who reached a DMR, 461 (51%) lost it: the loss of response after >2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with <MR2, P = .038).
In conclusion, reaching ≥MR2 and a MR3 at 3 months it seems predictive of a DMR at any time point. Considering the prerequisite for a discontinuation with a sustained DMR only a minority of patients can be eligible for the discontinuation, regardless the frontline treatment received.
在过去十年中，酪氨酸激酶抑制剂（TKIs）提高了达到深度且持续分子反应（DMR，定义为稳定的MR4和MR4.5）的慢性髓性白血病（CML）患者的总生存期（OS）。这些患者可能尝试停药。在我们的分析中，我们报告了在一大群慢性期CML患者中，由于反应时间和用作一线治疗的不同TKI而导致的 eligibility标准差异。
数据由LabNet CML导出，LabNet CML是GIMEMA于2014年建立的一个网络。该网络对分布在意大利各地的51个实验室之间的分子方法进行了标准化和统一，用于诊断和分子残留病（MRD）监测。
在分析的1777例患者中，774例有所有可评估的时间点（3、6和12个月）。在3个月时，40例患者达到≥MR4：其中14例（3.6%）使用伊马替尼，8例（5.8%）使用达沙替尼，18例（7.4%）使用尼罗替尼（P = 0.093）；在6个月时，146例患者处于MR4：42例（11%）使用伊马替尼，38例（28%）使用达沙替尼，66例（27%）使用尼罗替尼（P < 0.001）。在12个月时，231例患者实现了DMR：85例（22%）使用伊马替尼，55例（40%）使用达沙替尼，91例（38%）使用尼罗替尼（P < 0.001）。在3个月时达到至少≥MR2可预测在任何观察时间点的DMR：使用伊马替尼的患者中达到≥MR2的为67%，而<MR2的患者为30%，使用达沙替尼的患者中达到≥MR2的为66%，而<MR2的患者为28%，使用尼罗替尼的患者中达到≥MR2的为75%，而<MR2的患者为30%（P < 0.001）。在同一时间点上，达到至少≥MR3更能预测在任何时间点的DMR：使用伊马替尼的患者中达到≥MR3的为89%，而<MR3的患者为38%（P < 0.001），使用达沙替尼的患者中达到≥MR3的为84%，而<MR3的患者为40%（P < 0.001），使用尼罗替尼的患者中达到≥MR3的为89%，而<MR3的患者为49%（P < 0.001）。在达到DMR的908例患者中，461例（51%）失去了DMR：对于在3个月时达到≥MR2的患者，>2年后反应丧失显著（18%对<MR2的患者中的9.9%，P = 0.038）。
总之，在3个月时达到≥MR2和MR3似乎可预测在任何时间点的DMR。考虑到持续DMR停药的先决条件，无论接受何种一线治疗，只有少数患者有资格停药。
