Treatment of Severe Acute GvHD with Alemtuzumab Is Effective without Increased Relapse Rates

Abstract

Introduction Steroid-refractory acute graft versus host disease (GvHD) is still lacking a therapeutic standard and has a high mortality rate, thus presenting a major obstacle for allogeneic stem cell transplantation. Previously, we and others have demonstrated that the CD52 antibody alemtuzumab is able to significantly improve grade III and IV steroid-refractory acute GvHD (Schub et al., BMT 46, 143, 2011). However, this therapy results usually in complete lymphocyte depletion at least in the peripheral blood. This raises the question whether this may not also lead to a loss in tumor control. Here, we update and extend our previous monocentric observations in patients with severe steroid-refractory acute GvHD treated with alemtuzumab. Methods/ Patients Fifty-five consecutive patients (median age 52 years, range from 14 to 69 years)with lymphatic (n= 16) or myeloid (n= 39) malignancies that had received allogeneic stem cell transplantation from a family or unrelated donor developed severe acute GvHD that was refractory to high-dose corticosteroids. Patients were treated between the years 2004 and 2018 with alemtuzumab. While initially total doses up to 191 mg of alemtuzumab were applied, it became obvious that smaller doses were sufficient. Usually doses of 3 to 10 mg (first application limited to 3 mg) were given initially and alemtuzumab was repeated in intervals of 7 to 14 days for 3 to 4 times. In addition, shortly after alemtuzumab application immune suppressive drugs other than calcineurin inhibitors could be discontinued. Results Treatment complications were infections, particularly in CMV-positive patients. Thirty-four patients, despite many temporarily improving, eventually died due to infections and/ or other complications of acute GvHD. However, 15 patients, almost 30%, achieved a long-term survival often with limited restraints and remain free of their initial malignant disease. Only 6 patients (10.9%) relapsed later. Conclusions These data indicate, that despite additional severe alemtuzumab-mediated immunosuppression and subsequent “rebooting” of the immune system, immunosurveillance against foreign hemato-lymphatic cells was sufficient to prevent relapse in most patients