Large granular lymphocytic leukemia (LGLL) is a chronic lymphoproliferative disease commonly manifesting as infiltration of large granular lymphocytes in the peripheral blood and bone marrow. Both T-cell LGLL and chronic lymphoproliferative disorder of natural killer cells are entities of LGLL with similar clinical courses. Researchers presented efficacy and safety data of a phase 2 trial evaluating treatment for LGLL with a combination regimen of thalidomide, prednisone, and methotrexate (TPM).1
Symptomatic patients with treatment-naïve LGLL received the TPM regimen of thalidomide 50 mg to 100 mg each night, prednisone 0.5 mg/kg to 1.0 mg/kg every other day, and methotrexate 10 mg/m2 per week. The TPM regimen was administered for up to 12 months until disease progression or until treatment was no longer tolerable. Following cessation of treatment with the TPM regimen, thalidomide maintenance continued for another year or until intolerance. A regimen of cyclosporine, with or without steroids, was set as the control. The control regimen consisted of cyclosporine 3 mg/kg/day to 5 mg/kg/day with or without prednisone 0.5 mg/kg/day to 1.0 mg/kg/day.
Between August 2013 and January 2020, a total of 28 patients were enrolled in the study. Median follow-up was 26 months. Of the enrolled patients, 25 (89%) achieved hematologic and symptomatic response. Of these, 21 (75%) achieved complete response and 4 (25%) achieved partial response. The median time to best clinical response was 6 months.
The 3-year progression-free survival (PFS) rate was 90%, and the 3-year overall survival rate was 92%. The median PFS time was not reached in the TPM group. Compared with the control group, the curative effect was better for patients in the TPM group, with an overall response of 89% compared with 49%, respectively. Complete response was achieved in 75% of patients in the TPM group compared with 20% in the placebo group.
The regimen was well-tolerated, and adverse effects were uncommon. Grade 1/2 nausea was reported in 2 patients and grade 3 nausea in 1 patient. Two patients had grade 1/2 constipation and 1 experienced grade 1/2 peripheral neuritis.
The combination regimen of thalidomide, prednisone, and methotrexate demonstrates efficacy greater than that of cyclosporine and steroid treatment, and with limited adverse events. The investigators report that a multicenter clinical trial has been initiated to validate these findings.
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