Phase i study of alemtuzumab for therapy of steroid-refractory chronic graft-versus-host disease

Sarah Nikiforow, Haesook T. Kim, Bhavjot Bindra, Sean McDonough, Brett Glotzbecker, Philippe Armand, John Koreth, Vincent T. Ho, Edwin P. Alyea, Bruce R. Blazar, Jerome Ritz, Robert J. Soiffer, Joseph H. Antin, Corey S. Cutler

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Steroid-refractory chronic graft-versus-host disease (cGVHD) carries a poor prognosis with no agreed upon algorithm for treatment. Because both B and T cells contribute to the pathophysiology of cGVHD, we conducted a phase I study in subjects with steroid-refractory cGVHD using the anti-CD52 antibody alemtuzumab to transiently deplete most mononuclear subsets. Three regimens were investigated in a 3+3 dose-escalation design: 3 mg × 6 (dose level 1), 3 mg × 1, then 10 mg × 5 (dose level 2) and 3 mg × 1, 10 mg × 1, then 30 mg × 4 (dose level 3) administered over 4 weeks. The maximum tolerated dose of alemtuzumab was dose level 2. Thirteen patients were assessable for toxicities, which were primarily infectious and hematologic. Rates of infectious complications in the first 12 weeks were 0% at dose level 1 (n = 3), 50% at dose level 2 (1 death, n = 6), and 75% at dose level 3 (2 deaths, n = 4). Of 10 patients assessable for response, 7 (70%) responded at 12 weeks, with a 30% complete response rate. Four subjects reduced steroid dose or discontinued an immunosuppressant at 12 weeks. The median decrease in steroid dose at 1 year was 61.6%. Infectious complications occurred predominantly in the first 3 months after therapy, but full B and T cell recovery took well over 12 months. Immunophenotypic profiling revealed early recovery by natural killer cells and relative sparing of CD4+ and CD8+ central memory T cell subsets. Our study indicates that therapy with alemtuzumab for steroid-refractory cGVHD is tolerable with close attention to dosing and may be active in subjects who have failed multiple therapies. The pattern of lymphocyte recovery after alemtuzumab will inform the biology and future therapy of cGVHD. The use of alemtuzumab in the context of therapy for cGVHD deserves study in larger phase II trials.

Original languageEnglish (US)
Pages (from-to)804-811
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Issue number5
StatePublished - May 2013

Bibliographical note

Funding Information:
Financial disclosure: Supported in part by Genzyme, Inc. , the Gateway for Cancer Research (grant no. P-06-005 ), and the National Institutes of Health (grant no. P-01 CA142106 ). C.C. is supported by the Stem Cell Cyclists of the Pan Mass Challenge . S.N. is supported by the Friends of Dana-Farber .


  • Alemtuzumab
  • Chronic graft-versus-host disease
  • Steroid refractory
  • Treatment


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