Alemtuzumab-related haemophagocyticlymphohistiocytosis: Negotiating the cytokine storm

ABSTRACT

Background/AimsAlemtuzumab is an efficacious therapy for relapsing remitting multiplesclerosis (RRMS) preventing neural damage and reducing relapse rateby up to 74%. Administered in 2 treatment cycles 12 months apart andauthorised for use in > 40 countries, it is a humanized monoclonalantibody selectively directed against the CD52 antigen of T- and BLymphocytes. Significant autoimmune effects of Alemtuzumab arereported 6-60 months post-treatment including secondary autoimmunity (40%), thyroid disease (18-26%), idiopathic thrombocytopenicpurpura (1-3%) and anti-glomerular basement membrane disease(1%). There are 2 case reports of haemophagocyticlymphohistiocytosis(HLH) in people with MS triggered byAlemtuzumab. HLH is a clinical syndrome of dysregulated, pathological overactivation of innate immunity leading to cytokinestorm, multi-organ failure and a very high mortality rate. Clinicalfeatures are difficult to distinguish from, and may coexist with, othersyndromes such as sepsis. Recognition requires a high index ofclinical suspicion and management through multidisciplinary teams(MDT) using immune suppression. Early recognition and treatmentimprove outcome.MethodsWe report a case of HLH in a 30-year-old female 1 year after her firstcycle of alemtuzumab (second cycle delayed due to COVID-19pandemic) for treatment of RRMS. She was well until presentation 2days post gadolinium-contrasted routine MRI head scan with headache, fever, bacterial pneumonia/empyema and acute kidney injury.Febrile episodes persisted despite antibiotics.ResultsInvestigations revealed hepatosplenomegaly, pancytopenia(Haemoglobin 80g/L, WBC 0.9x109/L, neutrophils 0.67x109/L, lymphocytes 0.14 X109/L, platelets 82x109/L), hypertriglyceridaemia(5.5mmol/L) and hyperferritinaemia (94023ng/ml). She fulfilled theHistiocyte Society HLH-2004 diagnostic criteria for HLH (H-score238). Initial treatment was IV methylprednisolone (1g) and intravenousimmunoglobulin (IVIG) 2g/kg. Ferritin levels initially decreased(66933ng/ml) but re-escalated (93912ng/ml) with clinical deterioration, necessitating additional treatment with subcutaneous Anakinra 4mg/kg(recombinant interleukin-1 receptor antagonist) alongside oralprednisolone 1mg/kg. There was rapid, sustained improvement withresolution of fever but ferritin levels remained highly elevated(45000ng/ml) and cytopaenia was slow to resolve. Marker T cellsubsets showed significant T cell depression presumably postalemtuzumab. MDT discussion locally and nationally through theHLH Across Speciality Collaboration (HASC) led to discharge withcareful outpatient monitoring. Further IVIG 2g/kg was administeredwhich led to complete resolution of HLH and treatment wean.