Graft vs host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with posttransplant cyclophosphamide (PT-Cy) plus a short course of cyclosporine A (CsA) improved rates of severe acute and chronic GVHD compared with standard mycophenolic acid (MPA) plus CsA, according to the results of a phase 3 trial published in the journal Blood Advances.

The current standard for immunosuppressive treatment to prevent GVHD is the combination of CsA and mycophenolate mofetil (MMF). Despite prophylaxis with this regimen, the incidence of acute and chronic GVHD is 30% to 50% and 40% to 60%, respectively. The aim of this trial was to determine if the PT-Cy plus CsA could improve these rates among patients who underwent a nonmyeloablative, matched related and unrelated peripheral blood allo-HSCT.

The phase 3 trial randomly assigned 151 patients undergoing allo-HSCT 2:1 to receive PT-Cy plus CsA or MPA plus CsA. The primary endpoint was incidence of grade 1-2 GVHD within 180 days of transplant. Secondary endpoints included time to acute GVHD or extensive chronic GVHD, GVHD-free, relapse-free survival (GRFS), overall survival, and progression-free survival.

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The combination of PT-Cy and CsA significantly reduced the incidence of grade 2 to 4 acute GVHD with a rate of 30% compared with 48% in the MPA plus CsA group at 6 months (HR, 0.48; 95% CI, 0.29-0.82; P =.007). There was no significant difference between the treatment groups for incidence of non-severe (grade 1-2) acute GVHD (38% vs 29%; P =.26).

The 2-year cumulative incidence of extensive chronic GVHD was also reduced, with a rate of 16% with PT-Cy plus CsA compared with 48% with MPA plus CsA (HR, 0.36; 95% CI, 0.21-0.64; P <.001).

The reduction in acute and chronic GVHD resulted in improved GRFS, with a 1-year rate of 21% with PT-Cy plus CsA compared with 45% with MPA plus CsA (P <.001).

Overall survival, progression-free survival, and relapse rates were similar between the arms during a median follow-up of 56.4 months.

The incidence of adverse events (AEs) was higher in the PT-Cy plus CsA arm at 61% compared with 42% in the MPA plus CsA arm.

At 3 years after transplant, the non-relapse mortality was estimated to be 10% and 14% in the PT-Cy and MPA arms, respectively (P =.51). Relapse occurred among a cumulative 32% of patients treated with PT-Cy plus CsA and 24% with MPA plus CsA (P =.27).

The authors concluded that “PT-Cy combined with a short course of CsA after nonmyeloablative matched allo-HSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD.”

Disclosures: This study was supported in part by Novartis. Please see the original reference for a full list of disclosures.


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;6:3378-3385. doi: 10.1182/bloodadvances.2021005847