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. 2024 Mar 15;14(1):45.
doi: 10.1038/s41408-024-01032-8.

PTCy versus ATG as graft-versus-host disease prophylaxis in mismatched unrelated stem cell transplantation

Olaf Penack  1   2 , Mouad Abouqateb  3   4 , Christophe Peczynski  3   4 , William Boreland  3   4 , Zafer Gülbas  5 , Tobias Gedde-Dahl  6 , Cristina Castilla-Llorente  7 , Nicolaus Kröger  8 , Mathias Eder  9 , Alessandro Rambaldi  10 , Francesca Bonifazi  11 , Igor Wolfgang Blau  12 , Matthias Stelljes  13 , Peter Dreger  14 , Ivan Moiseev  15 , Hélène Schoemans  3   16 , Christian Koenecke  3   9 , Zinaida Peric  3   17
Affiliations

PTCy versus ATG as graft-versus-host disease prophylaxis in mismatched unrelated stem cell transplantation

Olaf Penack et al. Blood Cancer J. .

Abstract

There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are used. In Europe, it is standard practice to use rabbit anti-thymocyte globulin (rATG) to reduce the high NRM and GVHD risks after MMUD alloSCT. As an alternative to rATG, post-transplantation Cyclophosphamide (PTCy) is in increasing clinical use. It is currently impossible to give general recommendations regarding preference for one method over another since comparative evidence from larger data sets is lacking. To improve the evidence base, we analyzed the outcome of rATG vs. PTCy prophylaxis in adult patients with hematologic malignancies undergoing first peripheral blood alloSCT from MMUD (9/10 antigen match) between Jan 2018 and June 2021 in the database of the European Society for Blood and Marrow Transplantation (EBMT). We performed multivariate analyses using the Cox proportional-hazards regression model. We included 2123 patients in the final analyses (PTCy, n = 583; rATG, n = 1540). p values and hazard ratios (HR) presented here are multivariate outcomes. Two years after alloSCT we found a lower NRM in the PTCy group of 18% vs. 24.9% in the rATG group; p = 0.028, HR 0.74. Overall survival in the PTCy cohort was higher with 65.7% vs. 55.7% in the rATG cohort; p < 0.001, HR 0.77. Progression-free survival was also better in the PTCy patients with 59.1% vs. 48.8% when using rATG; p = 0.001, 0.78. The incidences of chronic GVHD and acute GVHD were not significantly different between the groups. We found significantly lower NRM as well as higher survival in recipients of peripheral blood alloSCTs from MMUD receiving PTCy as compared to rATG. The results of the current analysis suggest an added value of PTCy as GVHD prophylaxis in MMUD alloSCT.

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Conflict of interest statement

OP has received honoraria or travel support from Gilead, Jazz, MSD, Novartis, Pfizer and Therakos. He has received research support from Incyte and Priothera. He is member of advisory boards to Equillium Bio, Jazz, Gilead, Novartis, MSD, Omeros, Priothera, Sanofi, Shionogi and SOBI. HS reports having received personal fees from Incyte, Janssen, Novartis, Sanofi and from the Belgian Hematological Society (BHS), as well as research grants from Novartis and the BHS, all paid to her institution. She has also received non-financial support from Gilead, Pfizer, the EBMT (European Society for Blood and Marrow transplantation) and the CIBMTR (Center for International Bone Marrow Transplantation Research). IM received honoraria or travel support from Novartis, Sanofi, SOBI, Takeda. CCL received honoraria or travel support from Gilead/Kite and Therakos. Consulting fees for advisory board from Gilead/Kite, Nektar Therapeutics. FB participated to AB and received speaker fees from NEOVII and SANOFI. PD reports consultancy for AbbVie, AstraZeneca, Beigene, BMS, Gilead, Miltenyi, Novartis, Riemser; speakers bureau for AbbVie, AstraZeneca, BeiGene, BMS, Gilead, Novartis, Riemser, Roche; research support from Riemser (all to institution).

Figures

Fig. 1
Fig. 1. Survival outcomes and relapse.
A Non-relapse mortality; B overall survival; C relapse incidence; D progression-free survival; E GVHD-free relapse-free survival.
Fig. 2
Fig. 2. Cumulative incidences of GVHD.
A Acute GVHD II–IV, B acute GVHD III–IV, C chronic GVHD all grades, D extensive chronic GVHD.
See this image and copyright information in PMC

References

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