Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial

Abstract

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.

Fig. 1

Study flowchart.

Fig. 2

Polymorphonuclear neutrophil (PMN) and platelet engraftment after transplantation with post- cyclophosphamide (PTCy) or with anti-thymocyte globulin (ATG).

Fig. 3. Clinical outcomes according to the use of post-transplant cyclophosphamide (PTCy) or anti-thymocyte globulin (ATG).

Relapse incidence (RI) (A), non-relapse mortality (NRM) (B), disease-free survival (DFS) (C), overall survival (OS) (D), graft-versus-host disease-free, relapse-free survival (GRFS) (E) according to the use of post-transplant cyclophosphamide (PTCy) or anti-thymocyte globulin (ATG).

Fig. 4. Cumulative incidence of GVHD.

aGVHD grade II-IV(A), aGVHD grade III-IV(B), cGVHD (C), cGVHD requiring systemic treatment (D) according to the use of post-transplant cyclophosphamide (PTCy) or anti-thymocyte globulin (ATG).