Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Full Text

Duke Authors

Cited Authors

  • Soiffer, RJ; Kim, HT; McGuirk, J; Horwitz, ME; Johnston, L; Patnaik, MM; Rybka, W; Artz, A; Porter, DL; Shea, TC; Boyer, MW; Maziarz, RT; Shaughnessy, PJ; Gergis, U; Safah, H; Reshef, R; DiPersio, JF; Stiff, PJ; Vusirikala, M; Szer, J; Holter, J; Levine, JD; Martin, PJ; Pidala, JA; Lewis, ID; Ho, VT; Alyea, EP; Ritz, J; Glavin, F; Westervelt, P; Jagasia, MH; Chen, Y-B

Published Date

  • December 20, 2017

Published In

Volume / Issue

  • 35 / 36

Start / End Page

  • 4003 - 4011

PubMed ID

  • 29040031

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2017.75.8177


  • eng

Conference Location

  • United States