Analyzing Real-World Outcomes of Emapalumab Treatment for Patients With Primary Hemophagocytic Lymphohistiocytosis

According to retrospective study REAL-HLH, the clinical characteristics, treatment patterns, and survival outcomes of emapalumab treatment across a diverse patient population with primary hemophagocytic lymphohistiocytosis (HLH) treated in a real-world setting were consistent with the pivotal phase 2/3 pHLH trial.

The use of emapalumab was found to improve laboratory parameters and overall survival, as well as serve as a bridge to hematopoietic stem cell transplantation (HSCT) among certain patients with primary HLH in real-world clinical practice.

Hemophagocytic lymphohistiocytosis syndrome is uncommon, serious, and hyperinflammatory. Emapalumab, a human monoclonal antibody treatment that neutralizes the proinflammatory cytokine interferon gamma, is currently approved in the US to treat primary HLH among patients with refractory, recurrent, or progressive disease.

“The REAL-HLH study was conducted to address the limited availability of data on emapalumab use in real-world clinical settings,” Shanmuganathan Chandrakasan, MD, Children’s Healthcare of Atlanta, Atlanta, Georgia and coauthors explained.

The retrospective REAL-HLH study was performed including data from 33 hospitals in order to analyze real-world treatment patterns and outcomes in patients treated with 1 or more dose of emapalumab between November 2018 and October 2021. In total, 46 patients met the primary HLH classification criteria.

Physicians used emapalumab for treating refractory (19 out of 46), recurrent (14 out of 46), or progressive (7 out of 46) [primary] HLH. At initiation of emapalumab, 15 of 46 patients were in the intensive care unit, and 35 of 46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (72.7%), ferritin (44.4%), fibrinogen (97.4%), platelets (84.8%), and absolute neutrophil count (88.9%).

The 12-month survival from emapalumab initiation for the entire cohort (N = 46) was 73.1%. There were no discontinuations because of adverse events. In this study, 42 (91.3%) patients were considered eligible for transplant, pre-transplant survival was 38 of 42 (90.5%), while 31 (73.8%) transplant-eligible patients proceeded to transplant, and 23 of 31 (74.2%) of those who received transplant were alive at the end of the follow-up period.

“In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with [primary HLH ]treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial,” Chandrakasan and colleagues conclude.

“Results from the exploratory analysis suggest a relationship between overall survival and the treatment setting in which emapalumab was initiated (ie, higher survival in the non-ICU setting vs the ICU setting),” they added. “Although there are many confounding factors, these results may support potential benefit of early initiation of emapalumab before development of organ damage requiring critical care.”

Study authors also noted that survival among patients who started treatment with at least 3 mg/kg of emapalumab was greater than those starting treatment at less than 3 mg/kg, indicating possible benefit to be gained by higher initial dosing. They added that future studies and further research are required to determine the accuracy of this possibility.

Source:

Chandrakasan S, Jordan M B, Baker A, et al. Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab. Blood Adv. Published online May 14, 2024.  doi:10.1182/bloodadvances.2023012217