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Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis.

ABSTRACT: Emapalumab is a fully human immunoglobulin G1 monoclonal antibody directed against interferon-γ (IFN-γ), which in November 2018 received the first global approval for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance to HLH therapy. This review will highlight the pathophysiology of primary HLH, the therapeutic rationale for use of IFN-γ-targeting therapy, and potential limitations to its broader use in the treatment of HLH.

SUBMITTER: Vallurupalli M

PROVIDER: S-EPMC8938935 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis.

Vallurupalli Mounica M Berliner Nancy N

Blood 20191101 21

Emapalumab is a fully human immunoglobulin G1 monoclonal antibody directed against interferon-γ (IFN-γ), which in November 2018 received the first global approval for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance to HLH therapy. This review will highlight the pathophysiology of primary HLH, the therapeutic rationale for use of IFN-γ-targeting therapy, and potential limitations ...[more]

PMID: 31537529

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Project description:ObjectiveRheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.MethodsREAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.ResultsFifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, nine (60.0%) had systemic juvenile idiopathic arthritis, and one (6.7%) had adult-onset Still disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most patients (9 of 15; 60.0%) initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10 of 15; 66.7%) disease. Most patients received HLH-related therapies before (10 of 15; 66.7%) and concurrently with (15 of 15; 100.0%) emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters, including absolute neutrophil count and absolute lymphocyte count (13 of 14; 92.9%), chemokine ligand 9 (9 of 11; 81.8%), and platelets and alanine transaminase (11 of 14; 78.6%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%.ConclusionEmapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.

Project description:IntroductionHaemophagocytic lymphohistiocytosis (HLH) is a severe disorder with high mortality. The aim of this review is to update clinical management of relapsed/refractory HLH in adults, with a focus on current and new therapies.MethodsWe searched relevant articles in Embase and PUBMED with the MESH term "hemophagocytic lymphohistiocytosis; refractory; relapsing; adult."ResultsOne hundred eight papers were found; of these, 22 were retained for this review. The treatment of HLH in adult is based on the HLH-94 regimen. The response rate is lower than in pediatric patients, and 20-30% are refractory to this therapy. DEP regimen and allogenic hematopoietic stem cell transplantation (HSCT) are associated with complete response and partial response in 27% and 49.2%, respectively. However, many patients fail to achieve a stable condition before HSCT, and mortality is higher in them. New drugs have been developed, such as emapalumab, ruxolitinib, and alemtuzumab, and they may be used as bridges to the curative HSCT. They are relatively well tolerated and have few or mild side effects. With these agents, the rate of partial response ranges from 14.2% to 100%, while the rate of complete response is highly variable according to study and medication used. The number of patients who achieved HSCT ranged from 44.8% to 77%, with a survival rate of 55.9% to 100%. However, the populations in these studies are mainly composed of mixed-age patients (pediatric and adult patients), and studies including only adult patients are scarce.ConclusionRelapsed or refractory HLH in adult patients is associated with poor outcome, and consolidation with HSCT may be required in some cases. Mortality related to HSCT is mainly due to active HLH disease before HSCT and post HSCT complications. New drugs, such as empalumab, ruxolitinib, and alemtuzumab are interesting since these agents may be used as bridges to HSCT with increases in the numbers of patients proceeding to HSCT and survival rate.

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Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis.

Publications

Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis.

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