Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: A case series

Eur J Haematol. 2021 May;106(5):654-661. doi: 10.1111/ejh.13593. Epub 2021 Feb 17.

Abstract

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome associated with mortality rates of up to 88%. Standard therapy with high-dose glucocorticoids and etoposide used in adults is extrapolated from pediatric trials, with significant toxicity in older patients and those with poor performance status. The JAK1/2 inhibitor ruxolitinib has recently gained attention as a treatment option for HLH due to its broad cytokine-modulating abilities and safety profile. Herein we report our center's experience using ruxolitinib in the treatment of adult-onset secondary HLH.

Case series: We report four patients with profound secondary HLH provoked by diverse triggers, including invasive pulmonary aspergillosis on background systemic lupus erythematosus, disseminated tuberculosis, and T-cell lymphoma treated with ruxolitinib as monotherapy or combination therapy in upfront and salvage settings.

Results: All four patients had rapid, sustained improvement in clinical status, inflammatory markers, and hematological cell counts followed by durable remission. Three patients developed manageable infectious complications postruxolitinib.

Conclusions: This series demonstrates the effective use of JAK inhibition with ruxolitinib to control pathological immune activation in critically ill patients with secondary HLH and otherwise limited therapeutic options. JAK inhibition is also an area of urgent investigation for the treatment of cytokine storm associated with COVID-19.

Keywords: adult; aspergillosis; cytokine storm; hemophagocytic lymphohistiocytosis; invasive pulmonary; lupus erythematosus; macrophage activation syndrome; ruxolitinib; subcutaneous panniculitis-like t-cell lymphoma; systemic; tuberculosis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • COVID-19 / complications
  • Combined Modality Therapy
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / etiology
  • Cytokines / blood
  • Female
  • Humans
  • Invasive Pulmonary Aspergillosis / complications
  • Janus Kinases / antagonists & inhibitors*
  • Lupus Erythematosus, Systemic / complications
  • Lymphohistiocytosis, Hemophagocytic / drug therapy*
  • Lymphohistiocytosis, Hemophagocytic / etiology
  • Lymphoma, T-Cell / complications
  • Male
  • Middle Aged
  • Nitriles
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • SARS-CoV-2
  • Salvage Therapy
  • Tuberculosis / complications
  • Young Adult

Substances

  • Cytokines
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Janus Kinases