Alemtuzumab for Severe Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease

Abstract

Acute graft-versus-host disease (aGVHD) still remains the main cause of morbidity and mortality after allogeneic stem cell transplantation. Moreover, patients who did not respond to first-line treatment with glucocorticosteroids have a very poor outcome. Some studies suggested that alemtuzumab (a humanized monoclonal antibody against the CD52 antigen) might be effective for treatment of refractory aGVHD. Here we report a single-center experience with alemtuzumab in refractory gastrointestinal aGVHD. From September 2009 to April 2012 at the Grenoble medical university center, 24 patients who had presented a refractory gastrointestinal aGVHD to corticosteroid, or after another immunosuppressive drug, were retrospectively analyzed. Most patients (n = 19) presented stage 4 gastrointestinal aGVHD. Response to treatment (either complete or partial) was observed in 15 patients (62.4%). The overall survival rate at 1 year for all patients was 33.3% (95% confidence interval [CI], 15.9% to 51.9%) and for responders, 53.3% (95% CI, 26.3% to 74.4%). Two patients died from infection, 5 patients from recurrent GVHD, and 1 from an uncontrolled post-transplant lymphoproliferative disorder.

A Prospective Study of Alemtuzumab as a Second-Line Agent for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation

“…The CR rate is somewhat comparable to other commonly used agents for SR-aGVHD in children, such as infliximab [26], basiliximab [27], and daclizumab [28], with CR rates of 56%, 53%, and 46%, respectively. The response that we observed to alemtuzumab is also comparable to rates noted in the adult literature, with overall responses ranging from 50% to 94% and CR rates ranging from 20% to 40% [15–21,29,30]. An additional possible benefit of alemtuzumab was that most patients who experienced a CR or PR were able to successfully wean off their high-dose steroids.…”

Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease

“…[70] In small studies of SR GVHD patients, alemtuzumab provides overall response rates from 62 to 83%, with overall survival of 33–70%. [71,72] As expected, infectious complications frequently develop.…”

Pharmacokinetics and immunological outcomes of alemtuzumab-based treatment for steroid-refractory acute GvHD

“…1,2 Alemtuzumab has been shown to have clinical activity in a number of small prospective and retrospective studies, but optimal doses remain unknown and survival remains poor, with deaths from both GvHD and infection contributing. [3][4][5][6][7][8] Critically, very little is known about alemtuzumab's pharmacokinetics and pharmacodynamics in this context, and therefore dosing is empirical, ranging from 10-50 mg in the first week, with or without repeat dosing at 10-30 mg every 1-4 weeks. [3][4][5][6][7] In order to better define the clinical outcome and develop a rational approach to alemtuzumab dosing in SR-aGvHD, we conducted a phase II clinical study in which we incorporated weekly pharmacokinetics and immunological monitoring.…”