Efficacy of ruxolitinib in the treatment of relapsed/refractory large granular lymphocytic leukaemia

Large granular lymphocytic (LGL) leukaemia is a rare chronic lymphoproliferative disorder characterized by an expansion of cytotoxic T or NK cells. Despite a usually indolent evolution, most patients will require a treatment over the course of the disease because of cytopenia or symptomatic associated autoimmune disorders. First-line treatment is based on immunosuppressive agents, namely cyclophosphamide, methotrexate and ciclosporin. However, relapses are frequent, and there is no consensus on the management of relapsed/refractory patients. The implication of the JAK/STAT pathway in the pathogenesis of this disease has prompted our group to propose treatment with ruxolitinib. A series of 21 patients who received this regimen is reported here. Ten patients (47.6%) were refractory to the three main immunosuppressive drugs at the time of ruxolitinib initiation. Ruxolitinib yielded an overall response rate of 86% (n = 18/21), including 3 complete responses and 15 partial responses. With a median follow-up of 9 months, the median response duration was 4 months. One-year event-free survival and 1-year overall survival were 57% and 83% respectively. Mild side effects were observed. Biological parameters, notably neutropenia and anaemia, improved significantly, and complete molecular responses were evidenced. This study supports ruxolitinib as a valid option for the treatment of relapsed/refractory LGL leukaemia. In a series of 21 heavily pretreated patients with relapsed/refractory large granular lymphocytic leukaemia, ruxolitinib given as a monotherapy leads to 86% overall response rate, with 3 complete responses, 15 partial responses and only 3 patients being refractory (stable disease). In this international multicentre retrospective study, a significant improvement in all blood parameters (haemoglobin level, absolute neutrophil count, platelets) was observed. The median progression-free survival was 24.1 months, and the median overall survival was not reached.image