Real-World Demographics, Clinical Characteristics, and Treatment Patterns of Patients Treated with Emapalumab for Primary Hemophagocytic Lymphohistiocytosis in the United States: The Real-HLH Study

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome caused by overactivation of the immune system due to overproduction of proinflammatory cytokines, particularly interferon gamma (IFNγ). Emapalumab, a fully human monoclonal antibody that binds to IFNγ and neutralizes its activity, was approved by the FDA in November 2018 for adult and pediatric patients with primary HLH (pHLH) with refractory, recurrent, or progressive disease or intolerance to conventional therapy. Since approval, real-world data are lacking on the use of emapalumab in patients with pHLH. The REAL-HLH study assessed real-world treatment patterns among US patients treated with emapalumab.

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

Results: Of 105 patients enrolled, 41 (39.1%) patients had a pHLH diagnosis (mean age [±SD; range], 6.0 [±8.0; 0.8-39.0] years). A majority of patients were male (56.1%) and non-white (61%). At diagnosis, mean age (±SD; range) was 4.7 (±7.9; 0.3-39.0) years, 10/41 (24.4%) patients had central nervous system involvement, and 23/25 (92%) patients with available data met at least 5 of 8 HLH-2004 diagnostic criteria. Genetic mutations known to cause pHLH were found in 35/38 (92.1%) patients with available data. FHL2-PRF1 (34.2%), FHL3-UNC13D (22%), and CHS-LYST (12.2%) were the most common genetic mutations. Furthermore, 21/41 (51.2%) patients presented with infection at diagnosis with viral infections (14/21; 66.7%) being the most common. At the time of emapalumab initiation, 32/41 (78.1%) of patients had received prior treatment for HLH, 13/41 (31.7%) were in the intensive care unit, and 9/41 (22%) were receiving supportive care such as mechanical ventilation, extracorporeal membrane oxygenation, vasopressors, or dialysis. Emapalumab was initiated for the treatment of refractory 15/41 (36.6%), recurrent 14/41 (34.2%), or progressive 6/41 (14.6%) disease. Median (interquartile range [IQR]; range) time to emapalumab initiation from HLH diagnosis was 30 (79; 2-759) days. Median (IQR; range) treatment duration with emapalumab was 66 (74.5; 1-523) days. Median (IQR; range) emapalumab starting dose was 1.4 (2.0; 0.8-9.8) mg/kg and cumulative treatment dose was 66.8 (100.8; 1.0-512.2) mg/kg. Median (IQR; range) maximum administered emapalumab dose was 3.8 (6.7; 0.8-11.2) mg/kg. Median (IQR; range) number of administered doses of emapalumab was 16.0 (13.0; 1-66). Overall, 38/41 (92.7%) patients with available data were considered for hematopoietic stem cell transplantation (HSCT) by their treating physician, and 28/38 (73.7%) were able to receive HSCT.

Conclusions: This is the first study describing real-world treatment patterns with emapalumab across a diverse pediatric and adult patient population with pHLH. Nearly three-fourths of HSCT eligible patients treated with emapalumab (73.7%) were able to proceed to HSCT, which is consistent with the results of the pivotal emapalumab clinical trial (NCT01818492).