Primary HLH is a rare, life-threatening immune disorder characterized by a hyperinflammatory state. In patients with primary HLH, interferon gamma (IFNy) is often markedly elevated and is considered the key cytokine driving the hyperinflammatory state. The treatment goal of primary HLH is to stabilize the disease by controlling the associated hyperinflammation to bring patients to transplantation, the only potential curative therapy. Conventional HLH therapy comprises immunochemotherapies (namely dexamethasone and etoposide), which, unfortunately, predispose patients to the development of opportunistic infections and toxicity. Emapalumab is a fully human, anti-IFNy monoclonal antibody that neutralizes IFNy. Currently, there is no regulatory precedent or validated response criteria for efficacy assessment to guide clinical trials in primary HLH. Thus, clinical objective response criteria were used to define the primary endpoint of ORR in the pivotal study of emapalumab in primary HLH [1]. These response criteria were defined based on the Histiocyte Society HLH diagnostic criteria [1], clinical considerations from the study’s Scientific Steering Committee, and available experience reported with conventional HLH treatments. Herein, we report on findings of a sensitivity analysis of ORR to emapalumab using various assessment criteria.
Overall response rate (ORR) with emapalumab in patients with primary hemophagocytic lymphohistiocytosis (HLH): results of a sensitivity analysis.
Simone Cesaro;
2020-01-01
Abstract
Primary HLH is a rare, life-threatening immune disorder characterized by a hyperinflammatory state. In patients with primary HLH, interferon gamma (IFNy) is often markedly elevated and is considered the key cytokine driving the hyperinflammatory state. The treatment goal of primary HLH is to stabilize the disease by controlling the associated hyperinflammation to bring patients to transplantation, the only potential curative therapy. Conventional HLH therapy comprises immunochemotherapies (namely dexamethasone and etoposide), which, unfortunately, predispose patients to the development of opportunistic infections and toxicity. Emapalumab is a fully human, anti-IFNy monoclonal antibody that neutralizes IFNy. Currently, there is no regulatory precedent or validated response criteria for efficacy assessment to guide clinical trials in primary HLH. Thus, clinical objective response criteria were used to define the primary endpoint of ORR in the pivotal study of emapalumab in primary HLH [1]. These response criteria were defined based on the Histiocyte Society HLH diagnostic criteria [1], clinical considerations from the study’s Scientific Steering Committee, and available experience reported with conventional HLH treatments. Herein, we report on findings of a sensitivity analysis of ORR to emapalumab using various assessment criteria.
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