Combination Daclizumab and Infliximab for Steroid Refractory Acute Graft-Versus-Host Disease.
Authors: Rager Alison , Goldstein Steven C. , Frey Noelle , Davis Jennifer , Vozniak Michael , Smith Jacqueline , Hexner Elizabeth , Loren Alison Wakoff , Luger Selina , Perl Alexander , Reshef Ran , Tsai Donald E , Stadtmauer Edward A. , Porter David 
Published: October 2019

Abstract
Abstract 4643
Systemic steroids are the mainstay of therapy for GVHD, but treatment failure is common. Inflammatory cytokines, including IL-2 and TNF-a, are important mediators of GVHD, and may be critical targets for therapy. Given the ineffective treatment options for patients (pts) with steroid-refractory GVHD (SR-GVHD) and the almost universally poor outcomes with available therapies, between June 2001-May 2008, we treated 22 patients with SR-GVHD with a combination of anti-cytokine therapy that included daclizumab and infliximab. Seventeen of these patients were evaluable for a retrospective review of detailed outcomes.
The median age was 48 years (range 35-63) and grafts were from HLA matched siblings (5), matched unrelated donors (9), 1 antigen mismatched unrelated donors (2), or cord blood (1). Indications for stem cell transplant (SCT) were acute leukemia (9), chronic myelogenous leukemia (1), lymphoma (5) chronic lymphocytic leukemia (1) and multiple myeloma (1). Most patients received methotrexate with either tacrolimus (14) or cyclosporine (CSA) (2) and 1 patient received CSA with steroids as initial GVHD prophylaxis. High dose steroids were started for acute GVHD a median of 39 days after transplant in 12 pts (range 25-119). Five additional patients developed SR-GVHD a median of 46 days (range 25-119) after donor lymphocyte infusion.
All patients had persistent or progressive acute GVHD despite 1mg/kg/day (4 pts) or 2 mg/kg/day (13 pts) of corticosteroids for a median of 8 days (range 5-26) and were treated for acute GVHD severity index B (3), C (10) or D (4). GVHD involved the skin in 9 pts, liver in 9 pts, and gut in 15 pts. Daclizumab was given at 1.5 mg/kg day 1 and 1 mg/kg day 4, 8, 15, and 22. Infliximab was given at 10 mg/kg day 1,8,15, and 22. Overall, 47% of patients responded to therapy. Four patients (24%) had complete resolution of symptoms and 4 (24%) had partial responses. The remaining 9 patients failed to respond, progressed or had a mixed response. Additional therapies were started in 7 patients. Similar to other available reports on SR-GVHD, survival was limited and all pts died at a median of 6.7 months (range 1.6-26) from transplant and 37 days from initiation of daclizumab/ infliximab (8 from infection, 5 from GVHD, 2 from relapsed disease, and 2 from other causes). Data from additional patients will be presented. Although this is a retrospective analysis, these results suggest 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.

Disclosures:
Off Label Use: Daclizumab and Infliximab were used to treat acute Graft versus Host Disease. Porter:Genentec: Spouse employed by Genentech, owned by Roche, manufacturer of daclizumab.