Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series

Objectives: To assess the efficacy and tolerance profile of rituximab in rheumatoid arthritis (RA)-associated large granular lymphocyte leukemia (LGLL). Methods: Multicenter retrospective case series. Inclusion criteria were RA defined by the ACKULAR 2010 criteria and LGLL defined by absolute LGL count >= 0.3 x 10(9)/L with evidence of an expanded clonal LGL population (flow cytometry, TCR-y polymerase chain reaction, or Stat3 mutation). Results: Fourteen patients (10 women, mean age 55.2 +/- 14.2 years) included; 13 were seropositive for anti-cyclic citrullinated peptides (n = 11) or rheumatoid factor (n = 10). LGLL diagnosis was made 9.5 [IQR: 3.25;15.5] years after RA diagnosis. Thirteen patients had T-LGLL. Rituximab was the first-line therapy for LGLL for 4 patients. Previous treatment lines included methotrexate (n = 7), cyclophosphamide (n = 2), cyclosporin A (n = 1), or granulocyte colony-stimulating factor (n = 4). Rituximab was used in monotherapy (n = 8) or associated to methotrexate (n = 3), granulocyte colony-stimulating factor (n = 2), or alkylating agents (n = 1). The number of rituximab cycles ranged from 1 to 11 (median 6), with high heterogeneity in dosing regimens. Median duration response after rituximab initiation was 35 [IQR: 23.5;41] months. The overall response rate was 100%: 8 patients experienced complete response (normalization of blood count and LGL <= 0.3 x 10(9)/L) and 6 experienced partial responses (improvement in blood counts without complete normalization). The tolerance profile was good, with no infectious complications. Conclusion: rituximab appears as a valuable therapeutic option for RA-associated LGLL. (C) 2020 Elsevier Inc. All rights reserved.