Abstract Details

Title Central Nervous System T Cell Lymphoproliferative Disease Following Treatment with Alemtuzumab

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-020

Objective To present the first reported case of isolated CNS T cell lymphoma as a complication of alemtuzumab.

Background Alemtuzumab is a humanized monoclonal antibody approved for treatment of relapsing-remitting multiple sclerosis (RRMS). It targets CD52 which is expressed on T and B lymphocytes, resulting in their depletion. While alemtuzumab is highly efficacious in the treatment of RRMS, there are several safety concerns, including infusion reactions, infections, malignancy, and secondary autoimmune disorders.

Design/Methods Case report.

Results A 41 year-old woman with RRMS treated with alemtuzumab developed progressive cognitive decline and visual loss approximately four months after her second infusion cycle. MRI brain revealed posterior confluent T2 hyperintensities with a linear enhancement pattern. CSF analysis revealed 71 white blood cells (70% eosinophils) with negative infectious and autoimmune studies including GFAP antibodies. Pathology from brain biopsy revealed a CD3+ T cell monoclonal lymphoproliferative process concerning for T cell lymphoma. Systemic malignancy was ruled out with bone marrow biopsy and PET-CT. She received treatment with rituximab, high dose methotrexate, procarbazine, vincristine, methylprednisone, and cytosine arabinoside but with little clinical improvement. MRI brain 6 months later revealed worsening perivascular enhancement and progression. Whole brain radiation for palliative measures provided minimal improvement and ultimately she succumbed to the disease.

Conclusions Despite being an efficacious therapy, alemtuzumab has potentially serious side effects including various reported malignancies. In the CAMMS223 study, three cases of cancer occurred including breast cancer, non-EBV-associated Burkitt’s lymphoma, and cervical cancer. In the extension study of this Phase II trial, another patient developed systemic Castleman disease (a prelymphomatous state resulting in the activation of plasma cells). Among all clinical studies (CAMMS223, CARE-MS I and II and extension studies), 29 out of 1,486 alemtuzumab treated-patients developed malignancies. To our knowledge, this is the first report of a case of isolated CNS T-cell lymphoma in the setting of alemtuzumab therapy.

Authors/Disclosures
Lindsay A. Horton, MD (UT Southwestern) PRESENTER	Dr. Horton has nothing to disclose.
Murtaza Khan, MD (University of Kansas Hospital)	Dr. Khan has nothing to disclose.
Douglas Ney, MD, FAAN	The institution of Dr. Ney has received research support from Orbus Therapeutics. The institution of Dr. Ney has received research support from Denovo Biopharma.
Bette DeMasters, MD (UCHSC)	No disclosure on file
Enrique Alvarez, MD, PhD (University of Colorado)	Dr. Alvarez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Alvarez has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Alvarez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene/BMS. The institution of an immediate family member of Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon.
Amanda L. Piquet, MD, FAAN (University of Colorado)	The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kyverna . The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Joe Jones Law Firm. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cortez & Associates. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Falk Waas. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. The institution of Dr. Piquet has received research support from Anokion. The institution of Dr. Piquet has received research support from UCB . The institution of Dr. Piquet has received research support from Foundation for Sarcoidosis. The institution of Dr. Piquet has received research support from Kyverna . Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Autoimmune Encephalitis Alliance (AEA) that is relevant to AAN interests or activities. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Stiff Person Syndrome Research Foundation (SPSRF) that is relevant to AAN interests or activities.

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