Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy

Haghikia, Aiden; Dendrou, Calliope A.; Schneider, Ruth; Grüter, Thomas; Postert, Thomas; Matzke, Mike; Stephanik, Heike; Fugger, Lars; Gold, Ralf

doi:10.1016/s1474-4422(16)30382-9

Cited by 62 publications

(66 citation statements)

References 4 publications

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“…After the second ATZ course, recovery in terms of delayed hyper-repopulation was found in all investigated B cell subtypes, although baseline values were eventually reached. Previous reports introduced the hypothesis of a B cell overshot associated exacerbation of CNS inflammation after ATZ treatment whereas others reported that ATZ is highly effective in B cell mediated MS (30,31). However, in our cohort, although the overshot was also observed, the B cell repopulation was not associated with disease exacerbation.…”

Section: Discussioncontrasting

confidence: 77%

Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis

et al. 2020

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Section: Discussioncontrasting

confidence: 77%

Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis

et al. 2020

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“…A recent report describes two cases of inflammatory CNS disease occurring 6 months following alemtuzumab for MS, with ring-enhancing lesions on MRI. A prompt response to Rituximab was observed, leading the authors to propose that the pathology was due to the emergence of B-cell driven autoimmunity (9). Histology was not obtained in either of these patients, and the MRI appearances are markedly different to our case.…”

Section: Discussioncontrasting

confidence: 66%

Alemtuzumab-related eosinophilic central nervous system vasculitis

et al. 2020

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/userguides/explore-bristol-research/ebr-terms/ Alemtuzumab-related Eosinophilic CNS VasculitisOliver.leach@nhs.net @oliveraleach 01752 432028 fax: keywords: multiple sclerosis vasculitis autoimmune alemtuzumab eosinophilic Abstract A 36 year old woman with relapsing remitting MS presented with right sided spasms, focal seizures and neuropsychiatric symptoms 10 months after her first course of alemtuzumab. MRI brain imaging revealed multiple foci of T2 hyperintensity. Subsequent blood and CSF testing for PML, vasculitis and infective causes was negative. A brain biopsy was performed, revealing a prominent perivascular inflammatory infiltrate with multiple immune cells including eosinophils, suggesting eosinophilic vasculitis. The patient was treated successfully with cyclophosphamide. The potential sequelae of alemtuzumab treatment are discussed; this treatable complication should be considered when tests for JC virus are negative. Background to case A 36 year-old female presented in 2005 with right arm clumsiness, and was diagnosed with relapsing remitting multiple sclerosis after imaging and CSF analysis (fig 1A). Three relapses occurred over the next five years, including optic neuritis and right-sided weakness, which responded well to steroids. Surveillance MRI in 2011 revealed new lesions, and glatiramer acetate was commenced in 2012. Due to adverse effects treatment was stopped, but after further relapses dimethyl fumarate was commenced in July 2014. In December 2014 she experienced another relapse; MRI demonstrated new cervical lesions.After MDT discussion, treatment was escalated to alemtuzumab, and she

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“…alemtuzumab, where SAI are seen in more than 30%. These side effects are attributed to an excessive repopulation of B cells accompanied by the depletion of (regulatory) T-cells [1, 5]. …”

Section: Discussionmentioning

confidence: 99%

Peripheral CD19+ B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders

et al. 2018

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BackgroundWith ocrelizumab another drug is available for the treatment of multiple sclerosis (MS). Little is known on the long-term use of ocrelizumab on immune cell subsets, and no surrogate markers are available. Rituximab (RTX) has been in off-label use for the treatment of MS, neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) for > 10 years.ObjectiveWe evaluated the long-term depletion and repopulation rate of peripheral CD19+ B-cells as a potential surrogate for the clinical outcome, and whether it may serve for dosage and time-to-infusion decision making.MethodsWe evaluated the CD19+ and CD4+/8+ T-cell counts in n = 153 patients treated with RTX (132 MS, 21 NMO/NMOSD). The dosages ranged from 250 to 2000 mg RTX. Depletion/repopulation rates of CD19+ B-cells as well as long-term total lymphocyte cell counts, were assessed and corroborated with EDSS, ARR (annualized relapse rate), MRI, and time to reinfusion.ResultsCD19+ B-cells’ repopulation rate significantly varied depending on the dosage applied leading to individualized application intervals (mean 9.73 ± 0.528 months). Low/absent CD19+ B-cell counts were associated with reduced ARR, EDSS, and GD+-MRI-lesions. Long-term B-cell-depleting therapy led to a transiently skewed CD4+/8+ T-cell ratio due to reduced CD4+ T-cells and absolute lymphocyte counts, which recovered after the second cycle.ConclusionOur data suggest that CD19+ B-cell repopulation latency may serve as surrogate marker for individualized treatment strategies in MS and NMO/NMOSD, which proved clinically equally effective in our cohort as evaluated by previous studies.

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Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy

Abstract: et al. Alemtuzumab versus interferon beta 1a as fi rst-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012; 380: 1819−28.

Cited by 62 publications

References 4 publications

Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis

Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis

Alemtuzumab-related eosinophilic central nervous system vasculitis

Peripheral CD19+ B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders

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