Emapalumab Treatment in Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis in the United States: A Retrospective Medical Chart Review Study

Abstract

Objective: Rheumatologic 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.

Methods: REAL-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.

Results: Fifteen 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%.

Conclusion: Emapalumab-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.

Figure 1

Emapalumab treatment patterns in patients with rheumatologic disease–associated HLH (n = 15) and the subset of patients with sJIA/AOSD (n = 10). (A) Time to emapalumab initiation from HLH diagnosis and duration of treatment with emapalumab. (B) Emapalumab dosing. ^aDate of diagnosis was missing for one patient. AOSD, adult‐onset Still disease; HLH, hemophagocytic lymphohistiocytosis; sJIA, systemic juvenile idiopathic arthritis.

Figure 2

Time to first normalization of laboratory parameters based on physician's assessment^a or defined laboratory value criteria in patients with rheumatologic disease–associated HLH (N = 15) and the subset of patients with sJIA/AOSD (N = 10). Time to first normalization of laboratory parameters based on physician's assessment in (A) patients with rheumatologic disease–associated HLH (N = 15) and (B) patients with sJIA/AOSD (N = 10). Time to achieving defined laboratory parameters in (C) patients with rheumatologic disease–associated HLH (N = 15) and (D) patients with sJIA/AOSD (N = 10). ^aNormalization of laboratory and biomarker values were based on physician report. *Last time point when data were available. ALC, absolute lymphocyte count; ALT, alanine transaminase; ANC, absolute neutrophil count; AOSD, adult‐onset Still disease; CXCL9, chemokine ligand 9; HLH, hemophagocytic lymphohistiocytosis; sCD25, soluble interleukin‐2 receptor α; sJIA, systemic juvenile idiopathic arthritis.

Figure 3

Treatment outcomes with HLH‐related therapies including emapalumab in patients with rheumatologic disease–associated HLH (N = 15) and the subset of patients with sJIA/AOSD (N = 10). Change in average daily glucocorticoid dose (glucocorticoid tapering) from the week preceding emapalumab initiation up to week 8 of emapalumab treatment in (A) patients with rheumatologic disease–associated HLH (N = 15) and (B) patients with sJIA/AOSD (N = 10). Average daily dose of glucocorticoid (mg/kg prednisone equivalent) is shown starting from the week preceding emapalumab treatment (week 0, day –6 to day 0), followed by week 1 (day 1 to day 7), week 2 (day 8 to day 14), week 3 (day 15 to day 21), up to week 8 (day 50 to day 56) from emapalumab initiation. One patient received prior glucocorticoid treatment but not during the week preceding emapalumab treatment. (C) HSCT in patients with refractory/recurrent disease. (D) Overall survival from time of emapalumab initiation. One patient did not receive glucocorticoid treatment during the first 8 weeks of treatment with emapalumab. AOSD, adult‐onset Still disease; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplantation; sJIA, systemic juvenile idiopathic arthritis.