LAUSR

Philadelphia, United States Introduction: T-LGLL is a rare, incurable disorder characterized by clonal proliferation of CD3+CD8+ T-cells that can result in severe neutropenia, anemia and even death. Given the rarity of this disease, there is limited clinical data describing the course of the disease and prognostic factors for survival to guide treatment approaches. Methods: This study was conducted at the OSU James-CCC with IRB approval. All patients with a diagnosis of T-LGLL at OSU prior to 1 October 2018 were included. T-LGL was defined by 2016 WHO criteria: a monoclonal T-cell receptor and CD3+CD8+ population on flow cytometry of at least 500 cells/mm. All pathology was reviewed by the investigators. Response rates were determined utilizing the criteria from the ECOG 5998 study. Univariate probabilities of overall survival (OS) were estimated utilizing the Kaplan-Meier method using IBM SPSS v 24.0. The log-rank test was utilized to assess for differences between groups for OS. Results: 60 patients, with median age of 64 years (range 30-87) were included in the analysis (Table). With a median follow-up time of 28 months, OS at 1, 3, 5, and 10 years was 94%, 82%, 72%, and 66%. There was a trend toward improved 5-year OS in patients with rheumatoid arthritis (RA) vs those without (88% vs 66%; p=0.138). Women had improved OS at 4 years when compared to men (87% vs 66%; p=.081), and there was a trend towards worse OS at 3-years for patients with LDH > 190 U/L (72% vs 86%; p=.139). There was no impact of age, cytopenia, lymphocyte count, concomitant hematologic malignancy or autoimmune disease, degree of anemia or neutropenia at diagnosis on OS. Eighty-percent (48/60) patients received first line treatment; with 63% receiving methotrexate (MTX). Overall response rate (ORR) to frontline MTX was 37%: 3 CR (10%) 8 PR (27%). Of 43 evaluable patients, the ORR to all frontline therapy was 16/43=37% (30% PR, 7% CR). Twenty-four (40%) of patients received a second line treatment. Ten received cyclophosphamide (Cy), with 8/10 having received prior MTX. The ORR for 6 patients with prior MTX treatment who received Cy was 75%. ORR in 24 evaluable patients for all second line therapies was 54% (9 PR, 4 CR). 13 patients received a third line or greater treatment, with the ORR 54%. Conclusion: In this large analysis of patients with T-LGLL, we observed impaired long-term survival, with worse OS in patients with high LDH or male sex. ORR to current agents at any stage of treatment is limited, with ORR around 40-50%, highlighting the need for novel therapeutics in this rare disease.