Contributions
Abstract: P605
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS) used in>20000 people with multiple sclerosis (pwMS) worldwide. Clinical use is complicated by infections and antibody mediated secondary autoimmune disease. CNS autoimmunity leading to severe neurological deterioration has been recently described. This may be a B-cell-mediated process causing either diffuse necrotizing leukencephalopathy (DNL) or acute disseminated encephalomyelitis (ADEM).
A 27 year old lady with aggressive RRMS for 8 years, initially treated with interferon and natalizumab, but untreated since 2014, had a 1st course of alemtuzumab in February 2017 without complication. In September 2017 she reported reactivation of genital warts and was treated with imiquimod.
In November 2017 she developed a significant deterioration in motor function, progressing to needing a wheelchair by 8/1/18, and became bedbound by 15/1/18. MRI showed >30 contrast enhancing tumefactive lesions across her brain and spinal cord. CSF protein was 1.48g/L, WCC 11/Cu.mm. CD19+B cell count was 152cells/cmm (within normal range (NR)) comprising 41% of total lymphocytes. CD3+T cell count was relatively low at 174cells/cmm (NR>700) comprising 46% of total lymphocytes. Infectious causes, including toxoplasmosis were excluded. She was treated with methylprednisolone (7g) and 5 sessions of plasma exchange (PLEX) providing transient stability. 6 days after PLEX she deteriorated, becoming anarthric and quadriparetic. A tracheostomy was needed due to impaired bulbar function. MRI appearances worsened, with even more enhancing lesions and widespread leukoencephalopathic changes. She was given rituximab (2.4g) and 5 more PLEX sessions. Repeat lymphocyte subsets after rituximab showed a CD19 B cell count of 1 and CD3+T cell count of 252 comprising 87% of total lymphocytes. She is recovering and can now talk, swallow and use her right arm.
B-cell mediated severe neurological deterioration (BCMND) is thought to occur as a result of rapid reproliferation of B cells without T cell regulation. Eight cases of BCMND after alemtuzumab have been reported and we think that similar mechanisms led to this presentation suggesting an overall risk of approximately 1/2000. The use of the immune stimulating treatment imiquimod may be relevant in this case, and doctors should avoid its use after alemtuzumab. Severe neurological disability and death from DNL is a risk without aggressive treatment
Disclosure: Niall MacDougall. I have received honoraria and/or funding to attend educational events from Biogen, Genzyme, Roche, Merck and Novartis in the past 3 years.
James Overell - Speakers fees / advisory fees / travel / hospitality (Roche, Biogen, Novartis, Teva, Merck, Medday, Allergan, Celgene, Genzyme)Research / departmental funds (Novartis, Biogen, Roche, Genzyme, Merck)
Paul Gallagher - has received travel and research funding from Sanofi-Genzyme and travel funding for educational meetings from Novartis and Biogen
Sarah Jane Martin has received educational travel grants for attending neurology conferences from Biogen and Merck.
Natasha Fullerton - nothing to disclose
Thomas Suslak - nothing to disclose
Kirsty Chaplow - nothing to disclose
Abstract: P605
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS) used in>20000 people with multiple sclerosis (pwMS) worldwide. Clinical use is complicated by infections and antibody mediated secondary autoimmune disease. CNS autoimmunity leading to severe neurological deterioration has been recently described. This may be a B-cell-mediated process causing either diffuse necrotizing leukencephalopathy (DNL) or acute disseminated encephalomyelitis (ADEM).
A 27 year old lady with aggressive RRMS for 8 years, initially treated with interferon and natalizumab, but untreated since 2014, had a 1st course of alemtuzumab in February 2017 without complication. In September 2017 she reported reactivation of genital warts and was treated with imiquimod.
In November 2017 she developed a significant deterioration in motor function, progressing to needing a wheelchair by 8/1/18, and became bedbound by 15/1/18. MRI showed >30 contrast enhancing tumefactive lesions across her brain and spinal cord. CSF protein was 1.48g/L, WCC 11/Cu.mm. CD19+B cell count was 152cells/cmm (within normal range (NR)) comprising 41% of total lymphocytes. CD3+T cell count was relatively low at 174cells/cmm (NR>700) comprising 46% of total lymphocytes. Infectious causes, including toxoplasmosis were excluded. She was treated with methylprednisolone (7g) and 5 sessions of plasma exchange (PLEX) providing transient stability. 6 days after PLEX she deteriorated, becoming anarthric and quadriparetic. A tracheostomy was needed due to impaired bulbar function. MRI appearances worsened, with even more enhancing lesions and widespread leukoencephalopathic changes. She was given rituximab (2.4g) and 5 more PLEX sessions. Repeat lymphocyte subsets after rituximab showed a CD19 B cell count of 1 and CD3+T cell count of 252 comprising 87% of total lymphocytes. She is recovering and can now talk, swallow and use her right arm.
B-cell mediated severe neurological deterioration (BCMND) is thought to occur as a result of rapid reproliferation of B cells without T cell regulation. Eight cases of BCMND after alemtuzumab have been reported and we think that similar mechanisms led to this presentation suggesting an overall risk of approximately 1/2000. The use of the immune stimulating treatment imiquimod may be relevant in this case, and doctors should avoid its use after alemtuzumab. Severe neurological disability and death from DNL is a risk without aggressive treatment
Disclosure: Niall MacDougall. I have received honoraria and/or funding to attend educational events from Biogen, Genzyme, Roche, Merck and Novartis in the past 3 years.
James Overell - Speakers fees / advisory fees / travel / hospitality (Roche, Biogen, Novartis, Teva, Merck, Medday, Allergan, Celgene, Genzyme)Research / departmental funds (Novartis, Biogen, Roche, Genzyme, Merck)
Paul Gallagher - has received travel and research funding from Sanofi-Genzyme and travel funding for educational meetings from Novartis and Biogen
Sarah Jane Martin has received educational travel grants for attending neurology conferences from Biogen and Merck.
Natasha Fullerton - nothing to disclose
Thomas Suslak - nothing to disclose
Kirsty Chaplow - nothing to disclose