Ruxolitinib for the treatment of lymphoma-associated hemophagocytic lymphohistiocytosis: A cautionary tale.

INTRODUCTION: Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by fever, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and pancytopenia. Three publications reported success with ruxolitinib, a Janus-associated kinase (JAK1/2) inhibitor. This therapy interrupts the production of cytokines associated with hemophagocytic lymphohistiocytosis, namely interferon-γ and interleukins 2, 6, and 10. CASE REPORT: We administered ruxolitinib to two patients with lymphoma-associated hemophagocytic lymphohistiocytosis who had failed standard treatment with dexamethasone and etoposide. MANAGEMENT AND OUTCOME: Patient #1 was started on ruxolitinib 10 mg BID, and titrated to 15 mg BID. All but two of the hemophagocytic lymphohistiocytosis criteria resolved within two weeks, and she was able to restart therapy for lymphoma. During her ruxolitinib taper, she again presented with relapsed hemophagocytic lymphohistiocytosis. She was taking 2.5 mg a day at the time. Despite salvage treatment, she died from the disease. Patient #2 was a diffuse large B-cell lymphoma patient who presented with hemophagocytic lymphohistiocytosis and was treated with chemoimmunotherapy and achieved a complete response (CR). Hemophagocytic lymphohistiocytosis symptoms relapsed, and he was treated with ruxolitinib. He developed relapsed lymphoma and unfortunately died. DISCUSSION: While treating the underlying lymphoma is a clear priority, the cytopenias and other symptoms of hemophagocytic lymphohistiocytosis complicate the delivery of this therapy. Hence, the use of ruxolitinib as a bridge to definitive therapy was appealing. However, we are concerned about the progression of lymphoma while these patients were taking ruxolitinib. Ruxolitinib may be controlling cytokine storm associated with hemophagocytic lymphohistiocytosis, while other aspects of the condition are progressing. Therefore, we would advise caution in its use in lymphoma-associated-hemophagocytic lymphohistiocytosis until more data are available.