Severe Coombs Positive Autoimmune Hemolytic Anemia after Alemtuzumab Infusion for Relapsing Remitting Multiple Sclerosis. What Can We Learn?

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.2331-2331
• Main Authors: Desai, Parth Anil, Romere, Chase Mathew, Nguyen, Linda, Saksena, Annapurna, Abdullah, Siddiqui J, Diaz, Adolfo E
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-112724

Background: Alemtuzumab (LemtradaTM) is a recombinant humanized anti-CD52 monoclonal antibody that targets T and B lymphocytes, monocytes and eosinophils. It is a Food and Drug administration (FDA) approved drug (approved in November 2014) for relapsing remitting multiple sclerosis (RRMS). Alemtuzumab is also being used occasionally for immune disorders like graft versus host disease (GVHD) and aplastic anemia as well as for B- chronic lymphocytic leukemia (B-CLL) (FDA approved) and sometimes as a part of conditioning regimen for solid and bone marrow transplantations (Campath-1H®). As an interesting paradox to its anti-immune effects, the most serious adverse effects of Alemtuzumab apart from infections are autoimmune effects (AE) (black box warning issued by FDA), affecting various organs mainly thyroid and bone marrow (mainly immune thrombocytopenia). Rare singular cases are emerging of autoimmune hemolytic anemia (AIHA) occurring months after Alemtuzumab infusion; therefore, herein we present the first case series along with review of all the reported cases of AIHA after Alemtuzumab infusion used for treatment of RRMS. Methods: We did a retrospective chart review of 4 cases of AIHA developing after Alemtuzumab infusion which included 3 cases from the CARE MS-I/II and CARE MS Extension trials (Randomized controlled trials comparing Alemtuzumab versus Interferon beta 1a) (courtesy Sanofi/Genzyme) and 1 case encountered at UT health San Antonio. Simultaneously, we did a literature search using multiple available online databases (PubMed, Ovid, MEDLINE and Cochrane Library) from January 1, 2010 to May 1, 2018 for AIHA associated with Alemtuzumab infusion and found additional 3 reported cases. All of the cases were Direct Antiglobulin test (DAT/Coombs) positive and no other cause of hemolysis was identified. All the analysis was descriptive and exploratory. Results & Discussion: Out of the total 7 cases reviewed, there were 4 males and 3 females. The common theme amongst all the cases was presence of coombs positive autoimmune intravascular hemolysis occurring 3-15 months (Mean±SD=10±3 months) after the last dose of Alemtuzumab (table 1). In 71% (5/7) of the cases hemoglobin dipped below 5gm/dl requiring multiple transfusions with 1 reported death due to multiorgan failure from complication of severe AIHA. 70% (4/6) cases where steroids were used were not responsive to them requiring the use of some other therapeutic interventions such as Intravenous Immuno