Anti–T-Lymphocyte Globulin and Chronic GVHD-Free Survival in Unrelated Myeloablative HCT
A double-blind phase III trial has shown no benefit of anti–T-lymphocyte globulin (ATLG) vs placebo on chronic graft-vs-host disease (GVHD)-free survival in patients undergoing human leukocyte antigen (HLA)-matched unrelated myeloablative hematopoietic cell transplantation (HCT). The study was reported by Soiffer et al in the Journal of Clinical Oncology. ATLG treatment was associated with poorer progression-free and overall survival. A number of prior open-label randomized studies had suggested a benefit with ATLG in reducing chronic GVHD with no adverse effect on survival.
Study Details
In the trial, 254 patients aged 18 to 65 years from 27 sites in North America and Australia with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated HCT were randomized to receive ATLG (n = 126) or placebo (n = 128). Patients received ATLG or placebo at 20 mg/kg/d on days –3, –2, and –1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary endpoint was moderate-severe chronic GVHD-free survival.
Survival Outcomes
The ATLG group had reductions in grade 2 to 4 acute GVHD (23% vs 40%, P = .004) and moderate-severe chronic GVHD (12% vs 33%, P < .001), but no significant difference in moderate-severe chronic GVHD-free survival vs placebo was observed (2-year estimate = 48% vs 44%, P = .47). The ATLG group had poorer estimated 2-year progression-free survival (47% vs 65%, P = .04) and overall survival (59% vs 74%, P = .034); on a multivariate analysis, hazard ratios were 1.55 (P = .026) for progression-free survival and 1.74 (P = .01) for overall survival.
The investigators concluded: “In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe [chronic] GVHD-free survival. Moderate-severe [chronic] GVHD was significantly lower with ATLG, but [progression-free and overall survival] also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.”
The study was supported by Neovii Biotech.
Robert J. Soiffer, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
