GvHD Prophylaxis

Tocilizumab for GvHD prophylaxis – a phase II study

William Drobyski and colleagues from the Medical College of Wisconsin (Milwaukee, WI, USA) conducted a phase II study reviewing the impact of tocilizumab on GvHD and transplant outcomes in allogeneic stem cell transplant recipients. Tocilizumab is a monoclonal antibody that blocks activity of interleukin-6 (IL-6). Experimental data has shown that a deficiency of IL-6 in donor T-cells prolongs survival in hematopoietic stem cell transplant (HSCT) recipients and decreases GvHD-related mortality.

All patients in this study (N = 35) received standard GvHD prophylaxis with tacrolimus and four post-transplant doses of methotrexate. Tocilizumab was administered at a dose of 8mg/kg, given Day -1, prior to HSCT. A second phase to this study was to compare tocilizumab treated outcomes to historical control patients (N = 130) obtained via the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The aims of this study were to determine the impact of tocilizumab, in addition to standard immunosuppression on the incidence of GvHD and transplant outcomes.

Key findings:
  • N = 35 tocilizumab + standard therapy patients
  • Median age = 66 years (22–76 years)
  • Stem cell source
    • Bone marrow:17%
    • Peripheral blood: 83%
  • Median neutrophil engraftment:18 days (14–26)
  • Median platelet engraftment: 17 days (10–103)
  • Day +100 engraftment:
    • Median CD3 = 91% (43–100)
    • Median CD33 = 100% (91–100)
  • Day +100 aGVHD:
    • Grade II–IV: 14% (95% CI, 5–30)
    • Grade III–V:3% (95% CI, 0–11)
  • One-year transplant-related mortality (TRM):14% (95% CI, 5–28)
  • One-year relapse rate: 29% (95% CI, 15–44)
  • One-year disease-free survival (DFS): 57% (95% CI, 42–70)
  • One-year overall survival (OS): 68% (95% CI, 53–79)
  • Comparison to standard therapy patients
    • N = 130 case-matched historical controls
    • Day +180 GvHD; tocilizumab: 17% vs controls: 45%, HR = 0.34 (95% CI, 0.17-0.69), P = 0.003
    • Day +180 GVHD-free survival; tocilizumab: 69% vs controls: 42%, HR = 0.37 (95% CI, 0.21–0.67), P = 0.001
    • Chronic GVHD; tocilizumab: 38% vs controls: 45%, HR = 0.65 (95% CI 0.37–1.13), P = 0.13
    • There was no difference in TRM, relapse or DFS among the tocilizumab and control groups

This study showed that tocilizumab addition to standard immunosuppression yields benefits in terms of lower rates of aGvHD and GvHD-free survival. Even with these beneficial clinical findings, OS and TRM were not impacted in this investigation. The authors further highlighted that it is also encouraging to note that the clinical benefits were seen in an older transplant population, with a median age of 66 years. The clinical benefits in this small cohort merit further study regarding the potential role of tocilizumab in GvHD prophylaxis.

 

References
  1. Drobyski WR. et al. Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft versus host disease: low incidence of lower gastrointestinal tract disease. Haematologica. 2018. DOI: 10.3324/haematol.2017.183434.
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