Severe Relapse in a Multiple Sclerosis Patient Associated with Ipilimumab Treatment for Metastatic Melanoma (P2.231)

OBJECTIVE: We report a patient with long-standing, stable multiple sclerosis who presented with a severe relapse within days of treatment with ipilimumab for malignant melanoma. BACKGROUND: Ipilimumab is a humanized monoclonal antibody approved for the treatment of refractory malignant melanoma. The mechanism of action involves inhibition of CTLA-4, a T-cell surface molecule thought to limit lymphocyte activation, which has been implicated as a possible regulator of autoimmunity. T-cell mediated autoimmunity is thought to play a role in MS, and manipulation of the T-cell system in favor of a Th1 orientation might be expected to result in either worsening or amelioration of MS. Currently, colitis and dermatitis are commonly reported complications. DESIGN/METHODS: A 56 year old male with previously stable relapsing remitting MS received ipilimumab as treatment for surgically refractory malignant melanoma. Within one month, he experienced worsening of his MS demonstrated by two clinical relapses and three enhancing lesions on MRI. RESULTS: At the time of his first relapse, MRI revealed an asymptomatic new left centrum semiovale enhancing lesion. Within weeks, he had a second relapse, and MRI revealed a DWI +, enhancing lesion in the right corona radiata. Follow up imaging revealed enlargement of this lesion and a second enhancing lesion in the right frontal lobe. Subsequent imaging showed resolution of lesions that corresponded with clinical improvement. CONCLUSIONS: Dysfunction of T-cell regulation through CTLA-4 has been implicated in the pathogenesis and progression of MS. While the use of ipilimumab has been cautioned in patients with autoimmune disease, this is the first case to demonstrate clinical and radiographic worsening of MS directly following administration of ipilimumab. In light of the patient’s significant worsening, the use of ipilimumab should be cautioned in the setting of metastatic melanoma with even stable, mild MS. Study Supported by: Disclosure: Dr. Gettings has nothing to disclose. Dr. Hackett has nothing to disclose. Dr. Scott has received personal compensation for activities with Novartis, Biogen Idec, Teva Neuroscience, and Genzyme Corp. Dr. Scott has received research support from the Pittsburgh Foundation.