Work

356: Phase-II Study of Infliximab for the Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) Following Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT)

Year: 2008

Type: article

Abstract: Introduction: Infliximab is a chimeric monoclonal antibody that binds with high affinity to the soluble and transmembrane forms of tumor necrosis factor-α, and inhibits their binding with the cellular receptors. A number of retrospective studies have shown activity of this drug in the treatment of steroid refractory acute (a) GVHD. We conducted a prospective phase-II trial of infliximab for prophylaxis of aGVHD following AHSCT. Methods: Selection criteria included age >20 yrs, sibling (Sib) or unrelated donor (URD) availability and myeloablative (MA) AHSCT for hematologic malignancies (except CML in 1st chronic phase and aplastic anemia). Prophylaxis for aGVHD consisted of infliximab (10 mg/kg/dose) given 1 day prior to starting MA conditioning and subsequently on days 0, +7, +14, +28 and +42, cyclosporine and methotrexate (15 mg/m2 day 1 & 10 mg/m2 days 3,6,11). Results: Nineteen patients (pts) were prospectively enrolled. There were 13 male and 6 female pts with a median age of 53 yrs (range 27–64 yrs). Diagnoses included AML/MDS (n = 11), NHL (n = 4) and ALL (n = 4). Donors included matched Sib (n = 14), matched URD (n = 4) and mismatched URD (n = 1). 15 pts received MA conditioning with busulphan/cyclophosphamide, while 4 received TBI. All pts received peripheral blood stem cells. Prospectively enrolled pts getting infliximab (IG) were compared with a matched control group (CG) (n = 30). Pts in CG were matched for age, diagnosis, donor type, HLA typing, GVHD prophylaxis, conditioning regimen and stem cell source with IG. Median number of CD34+ cells in IG and CG was 4.95 and 5.22 × 106 cells/kg of recipient respectively. Cumulative incidence of grade II-IV aGVHD in IG and CG was 25% and 35% respectively (p > 0.05). No difference was seen in days to onset of aGVHD between the two groups. Patient age, sex, donor type and conditioning regimen had no effect on the probability of response to infliximab. Rates of chronic GVHD in IG and CG were 84% and 61% respectively (p = 0.22). Pts in IG had significantly more fungal infections (n = 5) compared to CG (n = 1) (p = 0.02). Kaplan-Meier estimates of 3 yr overall survival for IG and CG were 31% and 38% respectively (p = 0.42). Estimates of 3 yr progression free survival are 59% and 56% in similar order (p = 0.68). Conclusion: In conclusion, infliximab does not reduce incidence of grade II-IV aGVHD compared to historic controls. It causes a significant increase in fungal infections and may increase the likelihood of chronic GVHD.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2007.12.366