真实世界中慢性髓系白血病根据基线风险和一线治疗的结局：来自意大利网络/CML校园的数据。

Chronic myeloid leukemia outcomes according to baseline risk and first-line treatment in real-world settings: Data from the Italian Network/CML Campus.

作者信息

Giai Valentina, Rosso Tiziana, Castagnetti Fausto, Pregno Patrizia, Bonifacio Massimiliano, Capodanno Isabella, Tiribelli Mario, Stagno Fabio, Caocci Giovanni, Gozzini Antonella, Luciano Luigiana, Galimberti Sara, Bocchia Monica, Patriarca Andrea, Lanzarone Giuseppe, Martino Bruno, Guella Anna, Scortechini Anna Rita, Fava Carmen, Fozza Claudio, Sica Simona, Di Renzo Nicola, Musto Pellegrino, Pastore Domenico, Maggi Alessandro, Pizzuti Michele, Antonia Melillo Lorella Maria, Carella Angelo Michele, Tarantini Giuseppe, Mele Anna, Calistri Elisabetta, Coppi Maria Rosaria, Saccona Fabio, Scalzulli Emilia, Battaglio Beatrice, Iezza Miriam, Bitetti Cinzia, Freilone Roberto, Rosti Gianantonio, Albano Francesco, Pane Fabrizio, Specchia Giorgina, Ciccone Giovannino, Saglio Giuseppe, Breccia Massimo

机构信息

Division of Haematology, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino, Torino, Italy.

Clinical Epidemiology Unit and CPO Piemonte, Città della Salute e della Scienza di Torino, Torino, Italy.

出版信息

Cancer. 2025 Jul 1;131(13):e35963. doi: 10.1002/cncr.35963.

DOI:10.1002/cncr.35963

PMID:40581844

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12206341/

Abstract

BACKGROUND

Improved outcome has been reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) in sponsored trials.

METHODS

This is a multicenter prospective cohort study of consecutive patients with newly diagnosed chronic phase CML from 19 regions in Italy. Baseline treatments and prognostic factors on time to first optimal molecular response (≥ molecular response 3, MR3), time to disease progression, time to death from CML, and overall survival (OS) were analyzed using multivariable Fine and Gray models.

RESULTS

The authors included 1433 CML patients: 49% (median age, 70 years) treated with frontline imatinib (IMA), and 51% treated with second-generation TKIs (2G-TKIs; median age, 52 years). EUTOS long-term survival (ELTS) was low in 68.1% of 2G-TKIs patients, compared to 50.4% of IMA patients. Faster molecular responses were observed with 2G-TKIs within the first 6 months and maintained thereafter (subhazard ratio [sHR], 1.31; 95% confidence interval [CI], 1.15-1.50). Female gender and low ELTS risk had faster time of response. Achieving major molecular response (MMR or MR3) was associated with reduced risk of progression at 6 and 12 months. Overall, 41 patients progressed without differences between IMA and 2G-TKIs. Intermediate and high risk ELTS showed higher risk of progression and death from CML. Twenty-two CML-related deaths (16.5%) occurred mostly in the first 2 years from diagnosis, higher in 2G-TKIs patients (sHR, 1.75; 95% CI, 0.52-5.87). OS at 5 years was 88% with no clear differences between IMA and 2G-TKIs treatment after adjustment for potential confounders.

CONCLUSIONS

The study confirms faster responses with 2G-TKIs compared to IMA but similar clinical outcomes and a strong prognostic effect of ELTS.

摘要

背景

在申办的试验中，接受酪氨酸激酶抑制剂（TKIs）治疗的慢性髓性白血病（CML）患者的预后有所改善。

方法

这是一项对来自意大利19个地区的新诊断慢性期CML连续患者进行的多中心前瞻性队列研究。使用多变量Fine和Gray模型分析了首次达到最佳分子反应（≥分子反应3，MR3）的时间、疾病进展时间、CML死亡时间和总生存期（OS）的基线治疗及预后因素。

结果

作者纳入了1433例CML患者：49%（中位年龄70岁）接受一线伊马替尼（IMA）治疗，51%接受第二代TKIs（2G-TKIs；中位年龄52岁）治疗。2G-TKIs患者中68.1%的EUTOS长期生存（ELTS）较低，而IMA患者中这一比例为50.4%。在最初6个月内观察到2G-TKIs的分子反应更快，且此后得以维持（亚风险比[sHR]，1.31；95%置信区间[CI]，1.15 - 1.50）。女性性别和低ELTS风险的反应时间更快。达到主要分子反应（MMR或MR3）与6个月和12个月时进展风险降低相关。总体而言，41例患者出现进展，IMA和2G-TKIs之间无差异。中高风险ELTS显示出更高的CML进展和死亡风险。22例CML相关死亡（16.5%）大多发生在诊断后的前2年，2G-TKIs患者中更高（sHR，1.75；95% CI，0.52 - 5.87）。调整潜在混杂因素后，IMA和2G-TKIs治疗的5年OS率为88%，无明显差异。