Background/Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome caused by overproduction of proinflammatory cytokines, e.g., interferon gamma (IFNγ). Secondary HLH (sHLH), a subtype of HLH, occurs with underlying disease or triggers (rheumatologic disease, malignancy, infection, or iatrogenic). Emapalumab, a fully human monoclonal antibody that neutralizes IFNγ activity, was approved by FDA in November 2018 for patients with primary HLH with refractory, recurrent, or progressive disease or intolerance to conventional therapy. Off-label use of emapalumab in sHLH has been reported. The REAL-HLH study assessed real-world treatment patterns among patients treated with emapalumab.

Methods: A retrospective medical chart review conducted across 33 US hospitals identified patients treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Data on the subpopulation of patients with sHLH extracted from time of emapalumab initiation to end of data availability, death, or study end (December 31, 2021) are presented.

Results: Of 105 patients enrolled, 57 (54.3%) patients had a presumed sHLH diagnosis (mean age [±SD; range] = 10.4 [7.6; 0.14-30] years). Majority of patients were non-white (63.2%) and male (52.6%). At diagnosis, mean age (±SD; range) was 9.3 (7.5; 0.12-27) years and 15 of 17 (88.2%) patients with available data met ≥5 of 8 HLH-2004 diagnostic criteria. Underlying disease or triggers were identified in 53 (93%) patients of which 22 (41.5%) had a single trigger and 31 (58.5%) had multiple triggers. Infections (60.4%), malignancy (34%), rheumatologic disease (20.8%), and iatrogenic (11.3%) were the most common associated triggers. Epstein-Barr virus (34.4%) was the most common infection. At time of emapalumab initiation, 91.2% of patients had received or were receiving other treatments for HLH, including corticosteroids; 62.5% of patients were in the intensive care unit. Emapalumab was mainly initiated for treatment of refractory (42.1%), progressive (29.8%), and recurrent (14.0%) disease. Median (range) time to emapalumab initiation from HLH diagnosis was 16.5 (1-2278) days. Median (range) treatment duration with emapalumab was 38 (1-397) days. Median (range) emapalumab starting dose was 1.1 (0.7-5.9) mg/kg and cumulative treatment dose was 21.3 (1-336.5) mg/kg. Median (range) maximum administered emapalumab dose was 2.3 (0.7-12.5) mg/kg.

Conclusion: This is the first study to report real-world treatment patterns with emapalumab use across a diverse patient population with sHLH. A pivotal clinical trial of emapalumab in patients with sHLH and underlying rheumatologic disease is ongoing (NCT05001737).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/real-world-demographics-clinical-characteristics-and-treatment-patterns-of-patients-treated-with-emapalumab-for-secondary-hemophagocytic-lymphohistiocytosis-in-the-united-states-the-real-hlh-study/