Introduction

Hemophagocytic Lymphohistiocytosis (HLH) is a rare, lethal hyperinflammatory syndrome. Trigger factors include genetic, auto-immunity, viral infections and blood cancers, commonly lymphoma. The IL1-antagonist anakinra is approved by NHS-England for HLH despite a paucity of data on response rates and survival, both overall and for individual triggers. We report outcomes for HLH treated with anakinra and steroids from the East Midlands in England (population ~4-5 million) which use unified clinical guidelines.

Methods

Cases of HLH treated with anakinra were identified using mandatory national drug commissioning forms. HLH diagnoses were confirmed using the H-score. Patient demographics, trigger factors, response to and duration of use of anakinra, and the use of later therapies for triggers were planned to be presented descriptively. Survival was analysed using Kaplan-Meier methods with overall survival (OS) considered as the start date of anakinra to date of death or last follow up with data follow up to 15th July 2024

Results

Between 1st March 2022 and 1st June 2024, 25 cases were identified. Two patients had 2 separate HLH episodes which were considered separately. Median age was 65 (25-79) years, and 11 (44%) were male and 14 (56%) female. The median H-Score prior to anakinra was 210 (178-363) and median ferritin 21,392ug/l (1,591-210,815). 14/23 (61%) had hemophagocytosis on bone marrow biopsy.

16 (64%) cases had prior blood cancer or were diagnosed at HLH presentation, including 9 (36%) lymphomas, 3 of which were EBV positive. Four (16%) had auto-immune disease, including three (12%) adult-onset Still's disease and one (4%) systemic lupus erythematosus. Three cases (12%) had EBV-related HLH with no proven lymphoma and 2 (8%) had no trigger identified. 13 (52%) had a history of immunosuppression, HIV (n=1), recent chemotherapy (n=7) and steroids (n=5).

The median time from hospital admission to anakinra was 10 days (1-41), and from HLH diagnosis to anakinra 1 day (0-13). All patients began anakinra at 2mg/kg/day s/c and 8 (32%) had dose escalations up to 8mg/kg/day. The median number of days of anakinra received was 10 (1-44). All 25 cases received concurrent corticosteroids and two (8%) received empirical etoposide and 13 (52%) later received treatment for specific triggers, 7 (28%) targeted chemotherapy (6/9 with lymphoma), 5 (20%) immunosuppression and 1(4%) anti-viral therapy. Thirteen (52%) patients were considered to have responded to empirical/directed treatment. 12/23 (52%) unique patients died, 7 (28%) directly due to HLH, with the majority of deaths occurring within one week of HLH diagnosis.

With a median follow up of 13 months, median OS for the whole cohort was 103 days with no deaths after this time; Patients with blood cancer had a median OS of 24 days, however, median OS for those with lymphoma was not reached (NR), in contrast with other blood cancers which was only 12 days. Only one lymphoma patient who received chemotherapy died. Patients without blood cancer had even better outcomes with median OS NR and only two deaths, both within three days of HLH diagnosis. Of these, one had EBV viraemia and one no trigger identified, so underlying blood cancer cannot be excluded. All patients with auto-immune triggers remain alive.

Conclusion

Preliminary data suggests anakinra results in excellent outcomes for HLH due to autoimmune disease and, likely by improving curative chemotherapy delivery, impressive outcomes for lymphoma associated. Outcomes for other HLH due to blood cancers appear extremely poor, in part related to underlying disease aggressiveness. Regional clinical guidelines across large geographical areas help address variation in physician awareness, diagnosis and management of HLH.

Disclosures

No relevant conflicts of interest to declare.

Off Label Disclosure:

Anakinra is not licensed for use in HLH. However, it is approved for this use by NHS England.

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2024
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