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. 2024 May;38(5):1156-1163.
doi: 10.1038/s41375-024-02225-7. Epub 2024 Mar 27.

ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?

Olaf Penack  1   2 , Mouad Abouqateb  3   4 , Christophe Peczynski  3   4 , William Boreland  3   4 , Nicolaus Kröger  5 , Matthias Stelljes  6 , Tobias Gedde-Dahl  7 , Igor Wolfgang Blau  8 , Thomas Schroeder  9 , Urpu Salmenniemi  10 , Alexander Kulagin  11 , Régis Peffault de Latour  12 , Stephan Mielke  13 , Robert Zeiser  14 , Ivan Moiseev  11 , Hélène Schoemans  3   15 , Christian Koenecke  3   16 , Zinaida Peric  3   17
Affiliations

ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?

Olaf Penack et al. Leukemia. 2024 May.

Abstract

There is a high risk of GVHD and non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) from unrelated donors. Prophylaxis with rabbit anti-thymocyte globulin (rATG) is standard in Europe but post-transplantation Cyclophosphamide (PTCy) is an emerging alternative. We analyzed outcomes of rATG (n = 7725) vs. PTCy (n = 1039) prophylaxis in adult patients with hematologic malignancies undergoing peripheral blood alloSCT from 10/10 antigen-matched unrelated donors (MUD) between January 2018 and June 2021 in the EBMT database. The provided P-values and hazard ratios (HR) are derived from multivariate analysis. Two years after alloSCT, NRM in the PTCy group was 12.1% vs. 16.4% in the rATG group; p = 0.016; HR 0.72. Relapse was less frequent after PTCy vs. rATG (22.8% vs. 26.6%; p = 0.046; HR 0.87). Overall survival after PTCy was higher (73.1% vs. 65.9%; p = 0.001, HR 0.82). Progression free survival was better after PTCy vs. rATG (64.9% vs. 57.2%; p < 0.001, HR 0.83). The incidence of chronic GVHD was lower after PTCy (28.4% vs. rATG 31.4%; p = 0.012; HR 0.77), whereas the incidence and severity of acute GVHD were not significantly different. GVHD-free relapse-free survival was significantly higher in the PTCy arm compared to the rATG arm (2 y incidence: 51% vs. 45%; HR: 0.86 [95% CI 0.75-0.99], p = 0.035). In the absence of evidence from randomized controlled trials, our findings support a preference for the use of PTCy in adult recipients of peripheral blood alloSCTs from MUD.

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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). RZ received speaker fees from Novartis, Incytem Neovii, MNK and Sanofi.

Figures

Fig. 1
Fig. 1. Survival outcome parameters and relapse.
A NRM; B Overall survival, C Relapse incidence, D Progression-free survival and E GVHD-free relapse-free survival. Cumulative incidences are shown.
Fig. 2
Fig. 2. GVHD outcome parameters.
A Acute GVHD grades II–IV; B Acute GVHD grades III–IV, C Chronic GVHD all grades and D Extensive chronic GVHD - Cumulative incidences are shown.
See this image and copyright information in PMC

References

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