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

Robert J. Soiffer, Haesook T. Kim, Joseph McGuirk, Mitchell E. Horwitz, Laura Johnston, Mrinal M. Patnaik, Witold Rybka, Andrew Artz, David L. Porter, Thomas C. Shea, Michael W. Boyer, Richard T. Maziarz, Paul J. Shaughnessy, Usama Gergis, Hana Safah, Ran Reshef, John F. Dipersio, Patrick J. Stiff, Madhuri Vusirikala, Jeff SzerJennifer Holter, James D. Levine, Paul J. Martin, Joseph A. Pidala, Ian D. Lewis, Vincent T. Ho, Edwin P. Alyea, Jerome Ritz, Frank Glavin, Peter Westervelt, Madan H. Jagasia, Yi Bin Chen

Research output: Contribution to journalReview article

65 Scopus citations

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 graftversus-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 23, 22, 21 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.

Original languageEnglish (US)
Pages (from-to)4003-4011
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number36
DOIs
StatePublished - Dec 20 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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., ... Chen, Y. B. (2017). 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 of Clinical Oncology, 35(36), 4003-4011. https://doi.org/10.1200/JCO.2017.75.8177