Emapalumab use in malignancy-associated hemophagocytic lymphohistiocytosis in the United States: The REAL-HLH study.

Malignancy-associated hemophagocytic lymphohistiocytosis (mHLH), a hyperinflammatory syndrome, has poor prognosis and no standard therapy. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-gamma, is approved for treating primary hemophagocytic lymphohistiocytosis (pHLH). REAL-HLH, a retrospective chart review conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with at least 1 dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with mHLH. Overall, 51/105 (48.6%) patients did not meet the pHLH classification criteria and were categorized as presenting with secondary HLH; 17/51 patients had underlying malignancy (mHLH). At HLH diagnosis, median age (range) was 15.0 (3.0-27.0) years, 6/14 (42.9%) patients with available data had a positive Optimized HLH Inflammatory index indicating pathologic inflammation; 9/17 (52.9%) had infections, and 10/17 (58.8%) received emapalumab in an intensive care unit. Emapalumab was primarily initiated for treating refractory (10/17; 58.8%) or progressive (3/17, 17.7%) disease. Most patients received HLH-related therapies before (16/17; 94.1%) and/or concurrent with (15/17; 88.2%) emapalumab. Most key laboratory parameters improved, and some (fibrinogen [11/13; 84.6%], absolute neutrophil count [6/10; 60%], and CXCL9 [7/8; 87.5%]), normalized or stabilized per physician assessment, following treatment with emapalumab-containing regimens. Overall survival at the end of follow-up and 12-month survival probability from emapalumab initiation were 23.5% and 22.1%, respectively. In conclusion, emapalumab-containing regimens improved or normalized most laboratory parameters in patients with mHLH. Future studies are warranted to establish appropriate emapalumab dosing and utility in this high-risk population.

Duke Scholars

Author Jennifer Ann Rothman Pediatrics, Hematology-Oncology