GvHD prophylaxis with tocilizumab in combination with CSA and MMF in cord blood transplantation: A phase II trial

Double-unit cord blood transplantation (dCBT) is the SoC for patients with high-risk hematologic malignancies and has shown improved PFS rates. However, dCBT has also been associated with higher rates of aGvHD. Tocilizumab (Toci), an interleukin-6 receptor blocker, has demonstrated efficacy in reducing aGvHD in early clinical studies.

Politikos et al. published results of a phase II trial assessing the efficacy and safety of tocilizumab in combination with CSA and MMF in the prevention of aGvHD in patients with acute leukemia post-dCBT in Blood Advances.¹

The Toci cohort (N = 45) included patients diagnosed with AML (n = 21), ALL (n = 12), MPAL (n = 3), MDS (n = 4), CML (n = 2), or NHL (n = 3) who were undergoing dCBT. The no Toci cohort comprised of historic controls who received dCBT (N = 39). The primary endpoint was the incidence of Grade 2–4 aGvHD at Day 100.

Key learnings²

The cumulative incidence of Grade 2–4 aGvHD (71% vs 82%; p = 0.11) and Grade 3–4 aGvHD (11% vs 23%; p = 0.13) were comparable between the Toci vs no Toci cohorts, respectively.

The Toci cohort showed a reduced cumulative incidence of pre-engraftment syndrome (38% vs 72%; p < 0.001) and Grade 1–4 lower GI aGvHD (16% vs 33%; p = 0.056) than the no Toci cohort.

While the Toci cohort showed a trend towards faster platelet recovery (HR, 1.55; 95% CI: 0.98–2.46; p = 0.06) compared with the no Toci cohort, it was associated with delayed neutrophil engraftment (HR, 0.6; 95% CI: 0.38–0.95; p = 0.028) and no survival benefit.

The incidence of GvHD was not considerably reduced by the Toci-based regimen. Further investigation is needed to identify alternative approaches to aGvHD prophylaxis post-dCBT.