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

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Authors: Soiffer, R. J.; Kim, H. T.; McGuirk, J; Horwitz, M. E.; Johnston, L.; Patnaik, M. M.; Rybka, W.; Artz, A.; Porter, D. L.; Shea, T. C.; Boyer, M. W.; Maziarz, R. T.; Shaughnessy, P. J.; Gergis, U; Safah, H.; Reshef, R.; DiPersio, J. F.; Stiff, P. J.; Vusirikala, M.; Szer, J.; Holter, J.; Levine, J. D.; Martin, P. J.; Pidala, J. A.; Lewis, I. D.; Ho, V. T.; Alyea, E. P.; Ritz, J.; Glavin, F.; Westervelt, P.; Jagasia, M. H.; Chen, Y. B.
Article Title: 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
Abstract: 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 lt; .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.
Journal Title: Journal of Clinical Oncology
Volume: 35
Issue: 36
ISSN: 0732-183X
Publisher: Unknown  
Journal Place: United States
Date Published: 2017
Start Page: 4003
End Page: 4011
Language: eng
DOI/URL:

10.1200/JCO.2017.75.8177
Notes: LR: 20171219; JID: 8309333; 0 (Antilymphocyte Serum); 0 (HLA Antigens); 0 (Immunosuppressive Agents); WM0HAQ4WNM (Tacrolimus); YL5FZ2Y5U1 (Methotrexate); 2017/10/19 06:00 [pubmed]; 2017/12/20 06:00 [medline]; 2017/10/18 06:00 [entrez]; ppublish