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

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 2 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).