ASH 2018: Emapalumab Safe and Effective in Pediatric Patients With Primary Hemophagocytic Lymphohistiocytosis
Results suggest this monoclonal antibody should have a substantial impact on disease prognosis
December 4, 2018—San Diego, California—In pediatric patients with primary hemophagocytic lymphohistiocytosis, the monoclonal antibody emapalumab offers substantial symptom improvement with an acceptable safety profile, according to the results of an open-label, phase II/III study presented here at the 2018 American Society of Hematology Annual Meeting & Exposition, which took place from December 1 to 4.
Emapalumab is the first monoclonal antibody developed specifically to treat primary hemophagocytic lymphohistiocytosis, working by neutralizing interferon-gamma, a cytokine implicated in the disease.
To assess the performance of emapalumab in the management of primary hemophagocytic lymphohistiocytosis, study investigators enrolled 34 patients with the condition at 14 medical centers across Europe and the United States. Of the children enrolled, the majority were less than 1 year old, and 27 had previously failed to respond to chemoimmunotherapy.
Researchers administered emapalumab intravenously twice weekly at a starting dose of 1 mg/kg (increased to up to 10 mg/kg) for 8 weeks alongside 5 to 10 mg/m2/day of dexamethasone. After 8 weeks, the researchers assessed patients for the study’s primary endpoint, which was overall response to treatment. The study was sponsored by Novimmune, manufacturers of empalumab.
The researchers defined response as normalization or a 50% improvement from baseline in several indicators of disease severity, including enlarged spleen, fever, central nervous system abnormalities, low platelet and neutrophil counts, and the presence of biomarkers including ferritin, fibrinogen, and CD25 in the blood.
The study met its primary endpoint, in that 70% of enrolled patients experienced a response. This response was substantially better than the prespecified null hypothesis, which called for a 40% response rate (one-sided P < .025).
The median time to overall response was 8 days. The median cumulative duration of response was 33.0 days in patients who had failed prior therapy and 35.5 days in all treated patients.
Specific signs and symptoms, such as fever, dissipated after a few days of treatment with empalumab for some patients who responded, and other improvements were observed before the end of the trial.
Study presenter Franco Locatelli, MD, of Bambino Gesu Hospital in Rome, Italy, concluded during a press conference that now “hematologists and pediatricians have a new effective option for controlling” primary hemophagocytic lymphohistiocytosis.
Because children born with primary hemophagocytic lymphohistiocytosis have few current treatment options, and because many children included in the trial had failed best available treatment, Dr. Locatelli suggested that the adoption of emapalumab therapy as a standard practice could significantly improve the prognosis for babies born with this condition.
Dr. Locatelli added that he hoped emapalumab therapy would bridge “a child to allogeneic hematopoietic stem cell transplantation, while sparing toxicities associated with conventional therapies.”
Most of the patients who received emapalumab during the course of the trial were subsequently able to proceed to allogeneic hematopoietic stem cell transplantation therapy and achieve positive clinical outcomes.
Adverse events encountered during the trial were generally mild, and emapalumab was well-tolerated. However, mild to moderate infusion-related reactions did occur in 27% of patients, and an infection possibly linked to suppression of interferon-gamma signaling occurred during the trial (disseminated histoplasmosis), but this infection resolved with appropriate treatment. Overall, 56% of patients receiving emapalumab experienced infections. There were no observed off-target effects.
The United States Food and Drug Administration approved emapalumab for the treatment of both pediatric and adult patients with primary hemophagocytic lymphohistiocytosis in November 2018. The drug is currently approved for use in patients with treatment-resistant, recurrent, or progressive disease, or in patients for whom conventional therapy is contraindicated.
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