Comparison of PTCy with antithymocyte globulin in patients with AML in the first CR undergoing allo-HSCT

The current European Society for Blood and Marrow Transplantation (EBMT) guidelines suggest that rabbit antithymocyte globulin (ATG) should be used for prophylaxis in patients undergoing matched-unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (allo-HSCT).¹ However, ATG treatment delays immune reconstitution and can result in increased infection, especially viral infections. Therefore, it is interesting to compare this treatment with posttransplant cyclophosphamide (PTCy), which has been successfully used as graft-versus-host disease (GvHD) prophylaxis after haploidentical allo-HSCT.

To compare the outcomes between ATG and PTCy as GvHD prophylaxis, Eolia Brissot and colleagues² retrospectively analyzed a population of patients with acute myeloid leukemia (AML) following allo-HSCT using 10/10 MUD in first complete remission (CR).

Methods and patients

This retrospective study from the Acute Leukemia Working Party of the EBMT used data from the EBMT registry.

Inclusion criteria included the following:

• Age ≥ 18 years
• Diagnosed with AML and undergoing HSCT in first CR from a 10/10 MUD
• Peripheral blood stem cells (PBSC) or bone marrow (BM) as stem cell graft source

The characteristics of the patients included in this study are shown in Table 1. The median follow-up period in the ATG group was 33.2 months (interquartile range, 17.6–52.7) compared with 20.5 months (interquartile range, 6.9−32.6) in the PTCy group (p < 0.001). Patients in the PTCy group were younger (median age 46 vs 56 years, respectively; p < 0.001) and had undergone allo-HSCT more recently (median year of allo-HSCT 2016 vs 2014, respectively; p < 0.001).

Patients received 5 mg/kg thymoglobulin in the ATG group.

Table 1. Patient baseline characteristics²

The current study defined the endpoints as cumulative incidence of acute GvHD (aGvHD) Grade 2–4 and chronic GvHD (cGvHD), leukemia-free survival (LFS), overall survival (OS), refined GvHD-free, relapse-free survival (GRFS), cumulative incidences of relapse (RI), and non-relapse mortality (NRM). The modified Glucksberg criteria³ was used to grade aGvHD while cGvHD was graded according to the revised Seattle criteria.⁴

Key findings

As shown in Table 1, it is apparent that patients in the PTCy group were younger and underwent HSCT more recently compared with the ATG group. Peripheral blood stem cells were used more often than bone marrow stem cells as the source of the stem cells.

Following univariate and multivariate analyses, no statistically significant differences were found between ATG and PTCy groups for OS, GRFS, RI, NRM, and LFS.

In total, 174 and 1,452 patients receiving PTCy and ATG, respectively, fulfilled the inclusion criteria. The conditioning regimen intensity was similar between the two groups, and additional immunosuppressive agents were used in 55% of patients in the PTCy group and 85% of patients in the ATG group.

While neutrophil engraftment at 100 days was similar between the two groups (PTCy compared with ATG: 98.8% vs 99.2%; p = 0.65), there was a significant difference in median time to neutrophil engraftment (PTCy vs ATG: 21 vs 18 days; p < 0.001).

A reduced-intensity conditioning regimen was associated with a lower risk of Grade 2–3 aGvHD, while a Karnofsky performance score < 90 correlated with a higher risk of aGvHD.

Lower probabilities of LFS, OS, and GRFS were associated with a diagnosis of secondary AML and the presence of adverse cytogenetics, irrespective of whether ATG or PTCy was used. Old age was also negatively associated with LFS and OS.

At 2 years, the RI and NRM rates were similar between the two groups (ATG vs PTCy, RI: 23.7% vs 25.2%; NRM: 16.7% vs 15.2%).

The cumulative incidence of aGvHD and cGvHD were not statistically different from one another at 3 years posttransplant.

In patients treated with PTCy, the main cause of death was disease recurrence (47% vs 39% for ATG). Infection was the cause of 17% of deaths in the PTCy group and 22% in the ATG group.

Conclusion

The results suggest that PTCy yields comparable outcomes compared with ATG as GvHD prophylaxis in patients with AML undergoing MUD allo-HSCT. Therefore, the authors suggest that PTCy can be considered as an alternative to ATG for these patients. In this study, the incidence of death caused by infection was similar between the two groups, however, due to the retrospective nature of the study, it was not possible to compare the cumulative incidence of infections, especially viral infections.

Further investigation into the impact of the number, type, and schedule of different immunosuppressive therapies used is required. A more detailed prospective analysis of the morbidity associated with the different treatments used would be beneficial.