Case Report: Treatment With Alemtuzumab May Prompt Severe CNS Disease

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Treatment with alemtuzumab for MS may trigger a severe CNS disease.
Treatment with alemtuzumab for MS may trigger a severe CNS disease.

Researchers have reported the first documented cases of a severe B-cell-mediated central nervous system (CNS) disease after treatment with alemtuzumab for multiple sclerosis (MS).

Alemtuzumab is approved as escalation therapy in patients with relapsing forms of MS refractory to 2 or more treatments.

In the correspondence, Aiden Haghikia, MD, of Ruhr-University Bochum in Germany, and colleagues detail the acute deterioration of 2 patients with MS.

Patient 1, a man aged 41 years, had previously received interferon beta-1a, mitoxantrone, glatiramer acetate, and dimethyl fumarate before being treated with alemtuzumab due to relapses and continued disease activity on MRI. Less than 5 months after the first infusion, the patient presented with severe dysarthria, apraxia, left-dominant tetraparesis, and cognitive symptoms, as well as 20 new T1-enhancing lesions — many of which were ring enhancing — on MRI. After treatment with methylprednisolone 7000 mg elicited no response, the patient underwent plasmapheresis and 1 cycle of immunoadsorption. The patient also received rituximab, a B-cell-depleting antibody, after which his clinical symptoms significantly improved and the lesions retreated.

Patient 2, a woman aged 25 years, had previously been treated with alternating courses of interferon beta-1a, natalizumab, and fingolimod due to presentations of depression and high anti-JC virus antibody index. Continued disease activity on fingolimod prompted a first course of treatment with alemtuzumab. Approximately 6 months after the first infusion, the patient presented with bilateral tetraparesis of the legs. She was initially treated with methylpredisolone 3000 mg, which led to some symptom improvement. More than 2 months later, the patient was readmitted with left-sided hemiataxia and hemihypesthesia, and was treated with methylprednisolone and plasma exchange. Symptoms reoccurred less than 2 months later and were treated with a high dose of methylprednisolone. A delayed follow-up MRI revealed contrast-enhancing lesions, including ring-enhancing lesions, after which the patient was treated with rituximab. Her symptoms improved and the patient has since been stable.

“Our findings of marked improvement of the patients after plasmapheresis and rituximab therapy indicate a predominantly B-cell-driven pathology,” the investigators wrote. “The exacerbated inflammation seen in our patients is consistent with the time frame in which B-cell repopulation and peripheral expansion occur following alemtuzumab treatment.”

While it is not clear whether the acute deterioration is associated with a progression of the MS disease course or a secondary CNS autoimmunity, the researchers did rule out a genetic or infectious etiology. Future cases or relapses after treatment with alemtuzumab should be evaluated with MRI for ring-enhancing lesions and be treated with plasmapheresis and rituximab to prevent permanent disability.

Disclosures: Dr Haghikia reports receiving speaker fees from Bayer Healthcare and Biogen Idec, and research grants from Genzyme. Dr Gold reports receiving speaker fees and board honoraria from Baxter, Bayer Schering, Biogen Idec, Chugai, CSL Behring, Genzyme, Merck Serono, Novartis, Talecris, Teva, and Wyeth, and grant support from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva.

Reference

Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy. Lancet Neurol. 2017;16(2):104-106.

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