Published on August 22, 2025
Phase 2 trial of cyclosporine-A, mycophenolate mofetil, and tocilizumab GVHD prophylaxis in cord blood transplantation
by Alex Kadhim
Researchers at Memorial Sloan Kettering Cancer Center have found the addition of tocilizumab, an interleukin-6 receptor blocker, to standard GVHD prophylaxis modestly reduces inflammation-related complications but does not improve survival outcomes in adults undergoing double-unit cord blood transplantation (dCBT). This phase 2 trial, published in Blood Advances, explored whether tocilizumab could lower the incidence of acute graft-versus-host disease (aGVHD), particularly in the gastrointestinal tract, a major site of post-transplant complications. While the addition of tocilizumab showed biologically meaningful trends, the study concludes that its benefits are insufficient to justify continued use in this setting.
The trial was designed to evaluate whether targeting IL-6 — a proinflammatory cytokine implicated in GVHD — could mitigate inflammatory complications following dCBT. Forty-five adult patients with hematologic malignancies were enrolled between 2018 and 2021 and received a single dose of tocilizumab on day −1, in addition to standard prophylaxis with cyclosporine-A and mycophenolate mofetil. Outcomes were compared against 39 historical controls who met identical eligibility criteria but did not receive tocilizumab. The primary endpoint was the incidence of grade 2–4 aGVHD by day 100 post-transplant. Secondary endpoints included engraftment kinetics, pre-engraftment syndrome (PES), progression-free survival (PFS), overall survival (OS), and gut microbiome composition.
The addition of tocilizumab significantly reduced the incidence of PES (38% vs 72%, P < .001) and was associated with a trend toward lower stage 1–4 lower GI aGVHD (16% vs 33%, P = .059), although the primary endpoint was not met (grade 2–4 aGVHD: 71% vs 82%, P = .11). Neutrophil recovery was delayed in the tocilizumab group (median 25.5 vs 22 days, P = .009), though platelet engraftment was slightly faster. There were no significant differences in 3-year transplant-related mortality (20% vs 15%, P = .5), relapse (16% vs 5%, P = .2), PFS (64% vs 77%, P = .2), or OS (71% vs 85%, P = .2). Microbiome analysis showed a significant reduction in Enterococcus abundance (P = .0053), suggesting potential anti-inflammatory effects. Despite these observations, the trial does not support further pursuit of tocilizumab in dCBT, underscoring the need for alternative strategies to reduce GVHD burden.
Reference:
Politikos I, Brown S, Fein JA, et al. Phase 2 trial of cyclosporine-A, mycophenolate mofetil, and tocilizumab GVHD prophylaxis in cord blood transplantation. Blood Adv. 2025;9(10):2570-2584.
http://doi.org/10.1182/bloodadvances.2024014177
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