PTCy, tacrolimus, and mycophenolate mofetil as GvHD prophylaxis

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 3–5 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.

Results

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*

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%).

Conclusion

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.