Preliminary efficacy and safety of golidocitinib in relapsed/refractory T cell and NK cell large granular lymphocyte leukemia

Abstract Backgroud: Large granular lymphocyte leukemia (LGLL) is a rare and incurable hematologic malignancy with minimal therapeutic advances in recent decades. Immunosuppressive therapy remains the standard first line treatment, including methotrexate, cyclosporine A, and cyclophosphamide. No standard of care is available for refractory or relapsed disease. Golidocitinib, a potent selective JAK1 inhibitor, has shown promising antitumor activity in relapsed/refractory peripheral T cell lymphoma. Aims To evaluate efficacy and safety of golidocitinib monotherapy in patients with relapsed/refractory T/NK-LGLL. Methods This open-label, prospective clinical study evaluates the feasibility, efficacy, and safety of golidocitinib in relapsed/refractory (r/r) indolent T/NK-cell lymphoma, including cutaneous T-cell lymphoma (CTCL), indolent T-cell lymphoma of the gastrointestinal tract and LGLL (NCT06716658). Patients received oral golidocitinib 150 mg once daily in 28-day treatment cycles. Treatment continued until documented disease progression, intolerable toxicity or consent withdrawal, with a maximum duration of 24 cycles. Primary endpoint is objective response rate (ORR). Herein, preliminary efficacy and safety data of T-LGLL cohort are presented at this conference. Results As of the database cutoff on July 29, 2025, 16 r/r T or NK LGLL were enrolled and received at least one cycle of golidocitinib treatment (T-LGLL, n=14; NK-LGLL, n=2). A summary of baseline characteristics is presented as follows: median age 60 years (range 43 to 74), 13 male patients (81.3%), 3 with B symptoms (18.8%), and 4 with splenomegaly (25%). Fifteen patients (93.8%) required intervention for cytopenias including transfusion dependent anemia (9 patients, 53%), anemia (4 patients, 23%), severe neutropenia (1 patient), severe thrombocytopenia (1 patient), and autoimmune hemolytic anemia (1 patient). STAT3 mutations were detected in 11 patients (65%). All patients had relapsed or refractory disease after prior immunosuppressive therapy. The median number of prior systemic therapy lines was 2 (range 1 to 4). Six patients had failed three or more prior lines including PI3Kδ inhibitor linperlisib and JAK1/2 inhibitor ruxolitinib. Among 13 efficacy evaluable patients, the ORR was 92.3%. Eight patients achieved hematologic complete response (61.5%). Among patients with baseline hematologic abnormalities, neutrophil counts normalized in 88.9% (8/9) of those with neutropenia, and hemoglobin levels improved in 78.6% (11/14) of anemic patients. Notably, responses were observed in all 3 evaluable patients lacking STAT3 mutations, including 2 complete responses and 1 partial response. After median follow up of 7.0 months, treatment discontinuations occurred in three patients due to progressive disease (2 patients) and adverse events (1 patient). Median progression free survival and median overall survival were not reached. Treatment related adverse events occurred in only two patients (12%): one experienced grade 2 herpes zoster with concurrent grade 1 oral ulcer; another one had reversible liver function abnormalities. All events resolved with supportive measures. Conclusion Golidocitinib monotherapy demonstrates compelling clinical activity, including 100% response among STAT3 wild type evaluable patients, and a favorable safety profile in heavily pretreated r/r T-LGLL patients. These results support its further development in this population with unmet medical needs.