Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD

Abstract

Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD, and may be critical targets for therapy. We retrospectively reviewed our experience using combination anti-cytokine therapy of daclizumab and infliximab. Seventeen evaluable patients had a median age of 47 years (range 35–63). The conditioning regimen was myeloablative in 13 and nonmyeloablative in 4 cases. GVHD occurred a median of 49 days after transplant in 12 patients (range 21–231) and a median of 46 days (range 25–119) after donor lymphocyte infusion in 5 patients. All patients had persistent or progressive GVHD despite 1–2 mg/kg/day of corticosteroids for a median of 7 days (range 2–26). They received combination daclizumab and infliximab for acute GVHD IBMTR severity index B (3), C (10) or D (4). 47% of patients responded; 24% had complete resolution of symptoms and 24% had partial responses. Survival was limited and all died a median of 6.7 months (range 1.6–26) from transplant and 35 days from initiation of daclizumab/infliximab. This retrospective analysis suggests that combination anti-cytokine therapy with daclizumab/infliximab has significant activity in SR-GVHD, but outcomes remain poor. New methods to prevent and treat GVHD are urgently needed.