Alemtuzumab for Treatment of Refractory Evans Syndrome

Background:

There are limited treatment options for refractory Evans syndrome. After steroids and splenectomy, rituximab has been used w/some success. Alemtuzumab, a humanized monoclonal antibody against CD52, has been reported in small series of autoimmune hemolytic anemia (AIHA), usually in pts w/an underlying B-cell disorder such as CLL, but does not appear to have been reported in Evans syndrome.

Methods:

Chart review of a single case.

Results:

A 53 year old Caucasian man was admitted in 12/2012 with severe AIHA and thrombocytopenia. He was originally diagnosed with ITP at age 19, treated with steroids and later a splenectomy, then at age 40 (1999) presented with severe AIHA and thrombocytopenia, and was diagnosed with Evans syndrome. This was refractory to steroids, IVIG, vincristine and cyclophosphamide, but responded to an immunoadsorption column; he relapsed in 2005 and 2007, each time with predominantly isolated severe thrombocytopenia, which was treated successfully each time with weekly x 4 rituximab. He relapsed again in 3/2010, treated again with rituximab w/resolution of thrombocytopenia, but with recurrence of severe AIHA: DAT+ (IgG); hgb nadir 4.8gm/dL; LDH 1916 IU, TBili 10.4 mg/dL (direct bilirubin 1.1); retic count peaked at 52%. The severe anemia was refractory to steroids, IVIG, cyclophosphamide and vincristine (immunoadsorption column no longer available in the U.S.). He was then treated with intravenous alemtuzumab (3mg x 1 day then 10mg x 1 day then 30mg 3x/week x 4 weeks). 3 weeks after starting alemtuzumab there was a response, with improvement in hemolysis parameters (LDH 632, TBili 1.4, retic count 1.6%) and anemia (hgb 8.5, without transfusion support). By 4 weeks there was a complete normalization of hemolysis parameters (LDH 199, Tbili 1.2, retic 1%) and continued hemoglobin improvement (9.1), which normalized by week 12.

He remained in remission for 10 months until he developed relapse of ITP in 5/2011, which was refractory to rituximab and was then started on romiplastin in 6/2011, with normalization of platelet counts.

He remained in remission until 11/2012 when he developed severe thrombocytopenia (plt=3k), refractory to increasing doses of romiplastin, and then developed severe AIHA in late 12/2012 (hgb nadir 4.5; LDH 1070; retic 26%) with persistent severe thrombocytopenia (plt=2k). He was re-started on alemtuzumab from 12/30/12 to late 1/2013, dosed as before, with near complete resolution of thrombocytopenia (plt incremented to 138k) and hemolysis (LDH 195, retic 5%) by week 4, with improvement in hgb (to 8.3).

He then relapsed with severe AIHA in mid 3/2013 (hgb 5.1) and was restarted on alemtuzumab; there was no response in hemolysis parameters so cyclosporine was added; alemtuzumab was stopped on 4/24/13; he was tried again on rituximab on 5/10/13. He developed worsening, refractory AIHA, with renal and hepatic failure and, unfortunately, passed away on 5/24/13.

During the alemtuzumab treatments he received prophylactic acyclovir, PCP prophylaxis and had weekly surveillance CMV DNA testing. He did not develop any CMV or other infectious complications.

Conclusions:

Alemtuzumab administration resulted in a complete response lasting 10 months (and 29 months for the severe AIHA) and a 2^nd near complete response lasting 2 months in a very heavily pretreated man w/Evans syndrome. Use of this medication should be considered as another treatment option in the management of refractory cases.