A 'Whack-A-Mole' B cell Depletion Strategy Mitigates Alemtuzumab-Associated Secondary Autoimmunity: A Case Report & Literature Review

Introduction -alemtuzumab is indicated in the treatment of relapsing forms of multiple sclerosis (RRMS) in adults, with prominent clinical and imaging disease activity, rapid disability and increased lesion load, despite disease-modifying treatment (DMT). With this anti-CD52 monoclonal antibody, there is an incidence of secondary autoimmunity of approximately 50% induced by B-cell hyperrepopulation (in the absence of adequate T cell supervision), including a population of unusual and pro-inflammatory CD20 T cells ("chimeric lymphocytes"). The therapeutic protocol "Whack-A-Mole" (WAM), used by Frohman and Frohman (EMF & TCF) aims to promote the reconstitution of cellular and humoral mechanisms of regulatory synchrony, as well as the depletion of the clonal frequency of "chimeric lymphocytes" that contribute to alemtuzumab-associated autoimmunity. We describe a 21-year-old patient with RRMS treated with alemtuzumab, associated with rituximab 100mg as part of the WAM protocol. WAM was administered when CD19+ cells approached 40-50% of baseline levels. Discussion - We describe the WAM protocol that aims to treat B-cell hyper-repopulation after the use of alemtuzumab, whereby the conventional protocol induces secondary autoimmunity, with thyroiditis being the most common disorder. Since 2015, Frohman & Frohman have been using the WAM protocol without any cases of secondary alemtuzumab-related autoimmune disorders, corroborating the hypothesis that this modified treatment protocol produces both a period of lasting remission and protection against the risk of secondary autoimmunity. Final Comments - The high incidence of alemtuzumab-associated secondary autoimmunity appears to be significantly mitigated if not summarily abolished with the employment of the WAM protocol in conjunction with the use of alemtuzumab as an MS disease modifying therapy. This important observation opens new hope for the safer utilization of this important MS therapy, and particularly in those patients that are refractory to other disease modifying agents.