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

Abstract

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 ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. Data are presented for the subset of patients with mHLH. Overall, 51 of 105 (48.6%) patients were categorized as having secondary HLH, of which 17 of 51 patients had HLH associated with an underlying malignancy (mHLH). At HLH diagnosis, the median age (range) was 15.0 (3.0-27.0) years, 6 of 14 (42.9%) patients with available data had a positive Optimized HLH Inflammatory index, indicating pathologic inflammation; 9 of 17 (52.9%) had infections; and 10 of 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. Treatment with emapalumab-containing regimens normalized most key laboratory parameters and maintained normal values for others (fibrinogen [11/13; 84.6%], absolute neutrophil count [6/10; 60%], and chemokine ligand 9 [7/8; 87.5%]) per physician assessment. 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 normalized, improved, or maintained normal values for most laboratory parameters in patients with mHLH. Future studies are warranted to establish appropriate emapalumab dosing and utility in this high-risk population.

Graphical abstract

Figure 1.

Distribution of patients with mHLH by type of malignancy (N = 17). MDS, myelodysplastic syndrome.

Figure 2.

Emapalumab treatment patterns in patients with mHLH (N = 17). (A) Time to emapalumab initiation from HLH diagnosis and treatment duration. (B) Emapalumab dosing.

Figure 3.

Change in average daily GC dose from baseline up to week 8 of treatment with emapalumab-containing regimens.∗^,†,‡ ∗One patient received an average daily dose of 70 mg/kg that remained constant during 8 weeks of treatment with emapalumab (data not shown). ^†Average daily dose of GC (mg/kg prednisone equivalent) starting from the week preceding treatment with emapalumab-containing regimens (week 0, day −6 to 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. ^‡Three patients received prior GC treatment, but not during the week preceding treatment with emapalumab-containing regimens; 1 patient did not receive GC treatment during the first 8 weeks of treatment with emapalumab-containing regimens.

Figure 4.

Treatment outcomes with emapalumab-containing regimens in patients with mHLH (N = 17). (A) Time to normalization of laboratory parameters.^†,§ (B) Emapalumab-containing regimens as a bridge to HSCT. (C) Overall survival from time of emapalumab initiation.^||†Laboratory parameters for which data were available for ≥50% of the study population. ^§Normalization of laboratory and biomarker values were based on physician report. ^||12-month survival probability from emapalumab initiation: 22.1%; overall survival: 23.5%. ∗Last time point when data were available. ^‡Missing response = 1. ALC, absolute lymphocyte count; ALT, alanine transaminase; ANC, absolute neutrophil count; PI, principal investigator.

Figure 5.

Key clinical characteristics, treatment patterns, and survival among patients with mHLH (N = 17). (A) By duration of treatment with emapalumab-containing regimens. (B) By overall duration in the study. ∗Subtype not reported. ^‡Cause of death related to the clinical condition (HLH) for which emapalumab was used as reported by the treating physician. "Initiation" indicates the time between HLH diagnosis and initiation of emapalumab-containing regimens. "Duration" indicates the period for which patients received emapalumab-containing regimens. Causes of death unrelated to emapalumab use were as follows: patient 3: bacterial sepsis; patient 4: multiple medical complications related to therapy, including asparaginase-related hepatopathy; patient 9: AML progression, infection; patient 12: suspected fungemia and end-organ failure; patient 13: septic shock with stenotrophomonas bacteremia, and fluid overload and severe acute respiratory distress syndrome; patient 15: refractory chronic graft-versus-host disease multisystem, gastrointestinal bleeding. LPD, lymphoproliferative disorder; MDS, myelodysplastic syndrome; Pt, patient.