Posttransplant Cyclophosphamide Plus Cyclosporine A Effectively Prevents Severe GVHD: HOVON-96 Trial

A recent study in Blood Advances found that posttransplant cyclophosphamide after nonmyeloablative matched allogeneic hematopoietic stem cell transplantation (alloHSCT) effectively prevents severe graft-versus-host disease (GVHD) and could allow for implementation of early posttransplant chemotherapy and immunotherapy to further reduce the relapse risk after alloHSCT.

GVHD is the most important complication of alloHSCT, according to the study. Severe GVHD is associated with excess nonrelapse mortality and reduced quality of life after alloHSCT.

Researchers performed this prospective randomized, multicenter, phase 3 trial to explore whether posttransplant cyclophosphamide combined with a short course of cyclosporine A would result in a reduction of severe GVHD and improvement of GVHD-free, relapse-free survival (GRFS) as compared with cyclosporine A and mycophenolic acid after nonmyeloabalative matched related and unrelated peripheral blood alloHSCT. 

A total of 160 patients were enrolled between October 2013 and June 2018 and randomized in a 1:2 ratio to  cyclosporine A and mycophenolic acid or posttransplant cyclophosphamide combined with a short course of cyclosporine A. Eventually, 151 patients received an alloHSCT. 

At 6 months, the cumulative incidence of grade 2 to 4 acute GVHD was 48% in the cyclosporine A and mycophenolic acid group vs 30% in the posttransplant cyclophosphamide plus cyclosporine A group (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.82; P = .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16%, respectively (HR, 0.36; 95% CI, 0.21 to 0.64; P < .001). 

The 1-year estimated GRFS was 21% in the cyclosporine A and mycophenolic acid group vs 45% in the posttransplant cyclophosphamide plus cyclosporine A group (P < .001). With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 groups

“In conclusion, [posttransplant cyclophosphamide] combined with a short course of [cyclosporine A] effectively prevents the occurrence of severe acute GVHD and chronic GVHD in patients after [nonmyeloablative]-matched alloHSCT with an acceptable toxicity profile,” concluded study authors.

Source:

Broers AEC, de Jong CN, Bakunina K, et al. Posttransplant cyclophosphamide for prevention of graft-versus-host disease: Results of the prospective randomized HOVON-96 trial. Blood Adv. 2022;6(11): 3378–3385. doi:10.1182/bloodadvances.2021005847