Cyclophosphamide regime reduces graft-versus-host disease after stem-cell transplantation 

5th July 2023

A cyclophosphamide-based regime significantly reduces the incidence of graft-versus-host disease (GVHD) after stem-cell transplant compared to standard prophylaxis, according to the findings of a recent phase 3 randomised trial.

Published in the New England Journal of Medicine, the researchers randomly assigned adults with haematologic cancers undergoing allogeneic haematopoietic stem-cell transplantation to receive either cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis).

The primary endpoint was set as GVHD-free, relapse-free survival at one year, assessed in a time-to-event analysis. Events were defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression and death from any cause.

This comes after a phase 2 trial confirmed that using tacrolimus with mycophenolate mofetil and post-transplantation cyclophosphamide was the most promising intervention for GVHD prophylaxis. 

Cyclophosphamide prophylaxis success

In the phase 3 trial, a total of 431 patients with mean age of 64.3 years (60.3% male) were included, of whom 214 were assigned to the experimental regime and followed for a median of 12 months.

The primary outcome was significantly more common in the experimental prophylaxis group (hazard ratio, HR = 0.64, 95% CI 0.49 – 0.83, p = 0.001). In fact, after 12 months, the adjusted GVHD-free, relapse-free survival was 52.7% with the cyclophosphamide regime and only 34.9% with standard prophylaxis. 

In addition, while there was less severe acute or chronic GVHD and a higher level of immunosuppression-free survival at 12 months, there were no substantial differences between the two groups for overall and disease-free survival, relapse and transplantation-related death.

Preventing GVHD

Combining a calcineurin inhibitor such as tacrolimus with methotrexate is standard therapy to prevent GVHD disease following marrow transplantation for leukaemia. Despite this, 30-50% of patients undergoing allogeneic haematopoietic-cell transplantation still develop acute GVHD.

Along with the latest phase 3 trial findings outlined above, emerging data suggests high-dose post-transplantation cyclophosphamide can safely and effectively limit GVHD.