Contributions
Abstract: EP1721
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Case history: A 19 year old Asian patient with known relapsing remitting multiple sclerosis (MS), presented with a very severe multifocal rebound relapse 10 months after his first Lemtrada infusion. He initially presented in September 2014 with left-sided weakness, paraesthesia and ataxia and was started on Avonex. He was switched to Lemtrada in July 2015 following a brain stem relapse and radiological progression. His lymphocyte recovery started within 2 weeks and his lymphocyte levels 6 months post Lemtrada were near normal. In mid-April 2016 he presented with slurred speech and drooping on the right side of his mouth. On 4th May 2016 he was admitted to hospital with progressive dysarthria, diplopia, unsteadiness, left sided facial and lower leg numbness. He was given high dose intravenous methylprednisolone but continued to deteriorate requiring intubation and ventilatory support. Serial MRIs showed active tumefactive MS with almost entire brainstem involvement as well as large hemispheric tumefactive lesions. He was given a further course of steroids, plasmapheresis and six doses of cyclophosphamide. Following this he stabilised radiologically and clinically and was eventually moved back to the ward. In August 2016 he was discharged to a rehabilitation hospital. Seven months following discharge he was reviewed in MS clinic and has shown remarkable recovery with a jerky smooth pursuit and inability to perform tandem gait. His EDSS is 2. His MRI of the brain showed almost complete resolution of the previously seen lesions.
Discussion and conclusion: Lemtrada is a humanized monoclonal anti-CD52 antibody that causes rapid and prolonged pan-lymphocyte depletion with relatively rapid and disproportionate B-cell repopulation. Our patient showed rapid lymphocyte reconstitution starting within 2 weeks of his Lemtrada infusion which potentially played a role. As suggested by Gold and colleagues this rare rebound inflammatory phenomenon could be B-cell driven. Cyclophosphamide effect on T cells is to induce apoptosis and rapid cell death as well as to supress antibody production. Our patient made a remarkable clinical and radiological recovery with relatively little neurological sequelae. Cyclophosphamide should be considered as a rescue therapy in cases of rapidly progressive rebound inflammatory disease post-Lemtrada. The role of B-cells in rebound disease post-Lemtrada should be explored further.
Disclosure:
Dr. Sonia Kumari: nothing to disclose
Dr. Gordon Mazibrada: has served at advisory boards for Biogen, Merck, Teva, Novartis, Genzyme and Roche and our MS department has received funding from those companies for research projects and service developments.
Abstract: EP1721
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Case history: A 19 year old Asian patient with known relapsing remitting multiple sclerosis (MS), presented with a very severe multifocal rebound relapse 10 months after his first Lemtrada infusion. He initially presented in September 2014 with left-sided weakness, paraesthesia and ataxia and was started on Avonex. He was switched to Lemtrada in July 2015 following a brain stem relapse and radiological progression. His lymphocyte recovery started within 2 weeks and his lymphocyte levels 6 months post Lemtrada were near normal. In mid-April 2016 he presented with slurred speech and drooping on the right side of his mouth. On 4th May 2016 he was admitted to hospital with progressive dysarthria, diplopia, unsteadiness, left sided facial and lower leg numbness. He was given high dose intravenous methylprednisolone but continued to deteriorate requiring intubation and ventilatory support. Serial MRIs showed active tumefactive MS with almost entire brainstem involvement as well as large hemispheric tumefactive lesions. He was given a further course of steroids, plasmapheresis and six doses of cyclophosphamide. Following this he stabilised radiologically and clinically and was eventually moved back to the ward. In August 2016 he was discharged to a rehabilitation hospital. Seven months following discharge he was reviewed in MS clinic and has shown remarkable recovery with a jerky smooth pursuit and inability to perform tandem gait. His EDSS is 2. His MRI of the brain showed almost complete resolution of the previously seen lesions.
Discussion and conclusion: Lemtrada is a humanized monoclonal anti-CD52 antibody that causes rapid and prolonged pan-lymphocyte depletion with relatively rapid and disproportionate B-cell repopulation. Our patient showed rapid lymphocyte reconstitution starting within 2 weeks of his Lemtrada infusion which potentially played a role. As suggested by Gold and colleagues this rare rebound inflammatory phenomenon could be B-cell driven. Cyclophosphamide effect on T cells is to induce apoptosis and rapid cell death as well as to supress antibody production. Our patient made a remarkable clinical and radiological recovery with relatively little neurological sequelae. Cyclophosphamide should be considered as a rescue therapy in cases of rapidly progressive rebound inflammatory disease post-Lemtrada. The role of B-cells in rebound disease post-Lemtrada should be explored further.
Disclosure:
Dr. Sonia Kumari: nothing to disclose
Dr. Gordon Mazibrada: has served at advisory boards for Biogen, Merck, Teva, Novartis, Genzyme and Roche and our MS department has received funding from those companies for research projects and service developments.