Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study

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<sup>2</sup> 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).

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2025-03-12
DOI
https://doi.org/10.1038/s41392-025-02164-4
Citations
7
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
11.38

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article

Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study

Rui Lyu, Wenjie Xiong, Yuxi Li, Yanshan Huang et al.
7 citations
Signal Transduction and Targeted Therapy
Chronic Lymphocytic Leukemia Research
11.38
article

Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study

Rui Lyu, Wenjie Xiong, Yuxi Li, Yanshan Huang, Qi Wang, Rui Cui, Gang An, Shuhua Yi, Yaqing Feng, Dehui Zou, Yuting Yan, Weiwei Sui, Jianxiang Wang, Yan Chen, Huijun Wang, Wei Liu, Yan Xu, Xiaoli Hu, Fei Li, Jingwen Sun, Zhijian Xiao, Tengteng Yu, Ying Yu, Lugui Qiu, Wenyang Huang, Tingyu Wang
article en
7 citations

Abstract

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<sup>2</sup> 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).

Signal Transduction and Targeted TherapyVol. 10(1)
Tianjin University of Technology (CN), Nanchang University (CN), Sun Yat-sen University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Tianjin First Center Hospital (CN), Tianjin Academy of Fine Arts (CN), Zoucheng People's Hospital (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), Institute of Hematology & Blood Diseases Hospital (CN), First Affiliated Hospital of Nanchang University (CN), Shanxi Datong University (CN), Tianjin Medical University (CN)
National Natural Science Foundation of China, Chinese Academy of Medical Sciences
Good health and well-being
Openalex Percentile: Top 2%
Chronic Lymphocytic Leukemia Research
11.38
DOIOpen Access PDFOpenAlex
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