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GvHD prophylaxis: A retrospective comparison of PTCy and ATG combinations

By Kreena Mistry

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Arnon NaglerArnon Nagler

Apr 2, 2024

Learning objective: After reading this article, learners will be able to cite a new clinical development in graft-versus-host disease.


In patients who undergo allogeneic hematopoietic stem cell transplantation, a combination of a calcineurin inhibitor plus methotrexate (MTX) is used as the standard regimen for graft-versus-host disease (GvHD) prophylaxis. During the phase III Bone Marrow Transplant Clinical Trials Network (BMT CTN) 1703 study (NCT03959241), the combination of posttransplant cyclophosphamide (PTCy) with tacrolimus (TAC) and mycophenolate mofetil (MMF) demonstrated lower incidences of severe acute GvHD, chronic GvHD, and better GvHD-free relapse-free survival when compared with the TAC/MTX combination for the prevention of GvHD.1,2 However, the control arm did not include antithymocyte globulin (ATG), which is commonly used as a GvHD prophylaxis.

During the 2024 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Aron Nagler presented real-world data evaluating posttransplant outcomes of PTCy or ATG combined with TAC or cyclosporine A (CsA), and with MMF or MTX for the prevention of GvHD.1 Here, we summarize the key points from the poster below

Study design1

  • This was a registry-based retrospective analysis of patients with acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation from matched siblings or 9─10/10 unrelated donors in first complete remission.
  • This study compared PTCy with TAC or CsA and MMF with ATG combined with TAC or CsA and MTX for GvHD prophylaxis.
  • Posttransplant outcomes were measured using statistical tests including a multivariate analysis which was adjusted for potential confounding factors using a Cox proportional-hazards regression model.

Key findings

  • In total, 6,050 patients were included in this retrospective study
    • 402 patients received PTCy with CsA or TAC and MMF
    • 5,648 patients received ATG with CsA or TAC and MTX
    • Patients in the PTCy with CsA or TAC and MMF group were younger, with a median age of 48.7 years, compared with the ATG with CsA or TAC and MTX group, in which patients had a median age of 51.5 years (p = 0.024)
  • The median follow-up was 23.4 months in the PTCy with CsA or TAC and MMF group and 41.8 months in the ATG with CsA or TAC and MTX group (p < 0.0001).
  • A similar incidence and severity of acute GvHD were observed in both the PTCy with CsA or TAC and MMF, and ATG with CsA or TAC and MTX cohorts (Figure 1).

Figure 1. Occurrence of acute GvHD in patients posttransplant*

ATG, antithymocyte; CsA, cyclosporin; GvHD, graft-versus-host disease; MMF, mycophenolate mofetil; MTX, methotrexate; PTCy, posttransplant cyclophosphamide; TAC, tacrolimus.
*Data from Nagler.1
 

 

  • Non-relapse mortality was significantly lower in the PTCy with CsA or TAC and MMF cohort compared with the ATG with CsA or TAC and MTX cohort; all other transplant outcome parameters were similar across both cohorts (Table 1).
  • GvHD was the cause of death for a similar number of patients in both the PTCy with CsA or TAC and MMF and the ATG with CsA or TAC and MTX cohorts (11.6% and 13.9%, respectively).

Table 1. Multivariate analysis for posttransplant responses*

 

Relapse

NRM

OS

HR
(95% CI)

p-value

HR
(95% CI)

p-value

HR
(95% CI)

p-value

PTCy with CsA or TAC and MMF vs ATG with CsA or TAC and MTX

0.99
(0.77–1.27)

0.93

1.57
(1.07–2.3)

0.022

1.18
(0.94–1.49)

0.16

ATG, antithymocyte; CI, confidence interval; CsA, cyclosporin; HR, hazard ratio; MMF, mycophenolate mofetil; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; PTCy, posttransplant cyclophosphamide; TAC, tacrolimus.
Statistically significant.
*Adapted from Nagler.1


Key learnings

  • When comparing outcomes for patients provided with PTCy-based prophylaxis (PTCy with CsA or TAC and MMF) and those provided with ATG-based prophylaxis (ATG with CsA or TAC and MTX) for the prevention of GvHD, NRM was significantly lower with the PTCy-based regimen, while all other transplant outcomes, including incidence and severity of GvHD were similar.

References

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