Yu Ying, Li Yuxi, Cui Rui, Yan Yuting, Li Fei, Chen Yan, Wang Tingyu, Hu Xiaoli, Feng Yaqing, Yu Tengteng, Huang Yanshan, Sun Jingwen, Lyu Rui, Xiong Wenjie, Wang Qi, Liu Wei, An Gang, Sui Weiwei, Xu Yan, Huang Wenyang, Zou Dehui, Wang Huijun, Xiao Zhijian, Wang Jianxiang, Qiu Lugui, Yi Shuhua
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Tianjin Institutes of Health Science, Tianjin, China.
Signal Transduct Target Ther. 2025 Mar 12;10(1):85. doi: 10.1038/s41392-025-02164-4.
Large granular lymphocytic leukemia (LGLL) is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells. Standard first-line immunosuppressive treatments have limitations, achieving complete remission (CR) rates of up to 50%. Immune system dysregulation is implicated in LGLL. Promising results for thalidomide, an immunomodulatory drug, combined with prednisone and methotrexate (TPM), were observed in our pilot study. This multicenter study evaluated the efficacy and safety of a thalidomide, prednisone, and methotrexate (TPM) regimen in 52 symptomatic, methotrexate- and thalidomide-naive LGLL patients from June 2020 to August 2022. Thalidomide (100 mg daily for up to 24 months), prednisone (0.5-1.0 mg/kg every other day, tapered after 3 months), and methotrexate (10 mg/m weekly for up to 12 months) were administered. The primary objective was to determine the CR rate. The median follow-up duration was 29.0 months (range: 4.0-42.0). Forty-seven patients (90.4%) achieved hematological and symptomatic responses. Thirty-nine patients (75.0%) achieved CR. The median time to response was 3.0 months (range: 3.0-9.0). The median progression-free survival was 40.0 months (95% confidence interval (CI): 38.0-42.0), and the median duration of response was 39.0 months (95% CI: 36.1-41.9). The most common adverse event was peripheral neuropathy (24.1%), most of which (84.6%) were grades 1-2. Four patients experienced grade ≥3 adverse events. In conclusion, the TPM regimen was an effective and safe treatment for symptomatic LGLL patients, with a particularly high CR rate. This trial was registered at www.clinicaltrials.gov (#NCT04453345).
大颗粒淋巴细胞白血病（LGLL）的特征是细胞毒性T淋巴细胞或NK细胞的克隆性增殖。标准的一线免疫抑制治疗存在局限性，完全缓解（CR）率最高可达50%。免疫系统失调与LGLL有关。在我们的初步研究中，观察到免疫调节药物沙利度胺联合泼尼松和甲氨蝶呤（TPM）取得了有前景的结果。这项多中心研究评估了2020年6月至2022年8月期间，沙利度胺、泼尼松和甲氨蝶呤（TPM）方案在52例有症状、未使用过甲氨蝶呤和沙利度胺的LGLL患者中的疗效和安全性。给予沙利度胺（每日100mg，最多24个月）、泼尼松（每隔一天0.5 - 1.0mg/kg，3个月后逐渐减量）和甲氨蝶呤（每周10mg/m²，最多12个月）。主要目标是确定CR率。中位随访时间为29.0个月（范围：4.0 - 42.0）。47例患者（90.4%）获得血液学和症状缓解。39例患者（75.0%）达到CR。中位缓解时间为3.0个月（范围：3.0 - 9.0）。中位无进展生存期为40.0个月（95%置信区间（CI）：38.0 - 42.0），中位缓解持续时间为39.0个月（95%CI：36.1 - 41.9）。最常见的不良事件是周围神经病变（24.1%），其中大多数（84.6%）为1 - 2级。4例患者发生≥3级不良事件。总之，TPM方案是有症状LGLL患者的一种有效且安全的治疗方法，CR率特别高。该试验已在www.clinicaltrials.gov注册（#NCT04453345）。
