Emapalumab Received FDA Approval for Treating Hemophagocytic Lymphohistiocytosis

What Is Hemophagocytic Lymphohistiocytosis?

Hemophagocytic lymphohistiocytosis (HLH) is a rare hematological disease (originating in blood and bone marrow) involving uncontrolled hemophagocytosis caused by excessive release of substances called cytokines. First described in 1952 by James Farquhar, until 30 years ago its 5-year survival rates were around % 10, whereas today they are around % 70.

It has two forms: familial / primary and acquired / secondary:

• The familial form often presents in infancy, triggered by a viral infection, and is inherited in an autosomal recessive manner. Natural killer (NK) and CD8-positive T lymphocytes use the perforin/granzyme system, and various genetic defects affecting this system are responsible.
• Secondary hemophagocytic lymphohistiocytosis occurs without these known genetic mutations , alongside infection, malignancy (cancer) and autoimmunity involving abnormal activation of the immune system.

Both forms of hemophagocytic lymphohistiocytosis share diagnostic symptoms including fever, bicytopenia (low blood counts), hypertriglyceridemia (high blood fats) and/or hypofibrinogenemia, hyperferritinemia, hemophagocytosis, high blood levels of soluble interleukin-2 receptor (CD25), reduced or absent CD8+ T and NK cell activity, and splenomegaly (enlarged spleen).

The standard treatment chemotherapy and stem cell transplantationare used for hemophagocytic lymphohistiocytosis.

Emapalumab (Gamifant) in Standard Treatment of Hemophagocytic Lymphohistiocytosis with FDA Approval

On 20 November 2018, the US Food and Drug Administration (FDA), approved emapalumab (Gamifant), a monoclonal antibody binding and neutralizing interferon gamma, for adult and pediatric patients with primary (familial) hemophagocytic lymphohistiocytosis (HLH) refractory to current treatments, recurrent or progressive.

The multicenter, single-arm clinical trialthat brought FDA approval to emapalumab enrolled 27 pediatric HLH patients. All received an initial emapalumab dose every 3 days of 1 mg / kg. All also received dexamethasone (cortisone) at 5 to 10 mg / m2 / day. Before emapalumab, patients received prophylaxis (preventive treatment) against Herpes Zoster, Pneumocystis jirovecii and fungal infections.

The study found, an objective treatment response rate of % 63 (7 complete and 8 partial responses).

Among patients, in at least % 20, the most common adverse effects were infections, hypertension, infusion-related reactions (associated with administering the medicine into a vein) and pyrexia (fever).

The recommended initial emapalumab doseis an intravenous infusion twice weekly, over at least 1 hour, at 1 mg / kg. Doses after the initial dose may be increased according to clinical and laboratory findings.