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

Br J Haematol. 2024 Sep;205(3):915-923. doi: 10.1111/bjh.19476. Epub 2024 Apr 19.

Abstract

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.

Keywords: T‐cell lymphoma; chronic T cell leukaemia; clinical studies; lymphoproliferative disease; molecular biology.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Leukemia, Large Granular Lymphocytic* / drug therapy
  • Male
  • Middle Aged
  • Nitriles*
  • Pyrazoles* / therapeutic use
  • Pyrimidines* / therapeutic use
  • Recurrence
  • Treatment Outcome

Substances

  • Nitriles
  • Pyrazoles
  • ruxolitinib
  • Pyrimidines