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PTCy, tacrolimus, and mycophenolate mofetil as GvHD prophylaxis

Jan 17, 2023
Learning objective: After reading this article, learners will be able to cite a new clinical development in GvHD.

At the 64th American Society of Hematology (ASH) Meeting and Exposition, Holtan1 presented a late-breaking abstract on the phase III BMT CTN 1703 trial (NCT03959241), which we are pleased to provide a summary of here.

The trial investigated the novel combination of posttransplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for graft-versus-host disease (GvHD) prophylaxis, compared with the standard of care of Tac and methotrexate (MTX). The novel combination used in this study was selected as it was the best-performing novel combination in the previous BMT CTN 1203 trial.

Study design

The BMT CTN 1703 trial enrolled 431 patients across 37 centers in the US, who received reduced-intensity conditioning and peripheral blood stem cell grafts. The primary endpoint of this study was 1-year GvHD relapse-free survival (defined as Grade 35 GvHD, chronic GvHD that required systemic immunosuppression, relapse/progression of disease, or death). Patients were randomized 1:1 to either PTCy/Tac/MMF or TAC/MTX.


Baseline patient characteristics are shown in Table 1. The majority of patients had acute myelogenous leukemia as their primary disease and received a transplant from an unrelated donor.

Table 1. Baseline patient characteristics*

Characteristic, % (unless otherwise stated)









Median age (range), years

66.1 (20.178.6)

66.3 (26.377.4)

Primary disease



              Acute lymphoblastic leukemia



              Acute myelogenous leukemia



              Biphenotypic leukemia



              Chronic myeloid leukemia



              Myelodysplastic syndrome



              Lymphoma (all subtypes)



Donor type and HLA matching



              Related donor 6/6



              Unrelated donor 7/8



              Unrelated donor 8/8



Conditioning regimen












              Not transplanted



HLA, human leukocyte antigen; MMF, mycophenolate mofetil; MTX, methotrexate; PTCy, posttransplant cyclophosphamide; Tac, tacrolimus.
*Adapted from Holtan.1

Outcome measures

  • The primary endpoint of 1-year GvHD relapse-free survival was found to be significantly higher in patients receiving PTCy/Tac/MMF (52.7%) compared with patients receiving Tac/MTX (34.9%).
  • There were ten secondary outcomes measured. Among the secondary outcomes, GvHD-related outcomes are shown in Figure 1, with other outcomes shown in Figure 2.
  • Cumulative incidence of chronic GvHD at 1-year was significantly higher in patients treated with Tac/MTX than in patients treated with PTCy/Tac/MMF. Conversely, the cumulative incidence of Grade 2 infections at 12 months was significantly higher in the PTCy/Tac/MMF arm.

Figure 1. Disease-free survival and GvHD outcomes* 

aGvHD, acute graft-versus-host disease; cGvHD, chronic graft-versus-host disease; CI, cumulative incidence; MMF, mycophenolate mofetil; MTX, methotrexate; PTCy, posttransplant cyclophosphamide; Tac, tacrolimus.
*Adapted from Holtan.1


Figure 2. Other secondary outcome measures* 

aGvHD, acute graft-versus-host disease; CI, cumulative incidence; CMV, cytomegalovirus; IFS, immunosuppression-free survival; MMF, mycophenolate mofetil; MTX, methotrexate; PTCy, posttransplant cyclophosphamide; Tac, tacrolimus.
*Data from Holtan.1 

There were no differences in chimerism or rejection in the trial, with a graft rejection rate of 3% in the PTCy/Tac/MMF arm and 0.5% in the Tac/MTX arm. The most common cause of death was recurrent or persistent disease, affecting 39.6% of patients in the PTCy/Tac/MMF arm and 42.9% of patients in the Tac/MTX arm. Acute GvHD was a more common cause of death in the Tac/MTX arm (14.3%) compared with the PTCy/Tac/MMF arm (4.2%), whereas organ failure was a common cause of death in the PTCy/Tac/MMF arm (22.9%) compared with the Tac/MTX arm (10.7%).


Use of PTCy/Tac/MMF as GvHD prophylaxis produced a superior 1-year GvHD relapse-free survival compared with the current standard of care, due to reducing the occurrence of acute and chronic GvHD. Although treatment with PTCy/Tac/MMF increased Grade 2 infections, it did not cause an increase in Grade 3 infections, and the majority of infections occurred within the first month. Disease relapse was found to be similar across the arm; thus, Holtan concluded that PTCy/Tac/MMF should become the new standard of care in adult patients who are receiving reduced-intensity conditioning transplantation. Further analysis of patient-reported outcomes and microbiota studies are planned.

  1. Holtan S. Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil as the new standard for graft-versus-host disease (GVHD) prophylaxis in reduced Intensity conditioning: Results from phase III BMT CTN 1703. Oral abstract #LBA-4. 64th American Society of Hematology Annual Meeting and Exposition; Dec 13, 2022; New Orleans, US


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