Ptcy-ATG-CSA Vs. ATG-MMF-CSA for Gvhd Prevention for 10/10 HLA Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

Post-transplant cyclophosphamide (PTCY) combined with other immunosupressant agents has been a milestone in haploidentical-HCT (haplo-HCT). Secondary to its efficaty, it use is being expanded to allo-HCT performed from matched donors with notable success. However, despite that using PTCY out of the haplo-HCT setting is becoming prevalent, a standard drug combination has not been yet established.

The use of PTCY at a dose of 50mg/kg and administered on day 3 and 4, combined with 4.5mg/kg of anty-thymocyte globuline (ATG) and cyclosporine (CsA) (PTCY-ATG(4.5)-CsA) become our Institutional GVHD prophylaxis for 10/10 HLA-matched unrelated donor (MUD) peripheral blood (PB) allo-HCT in 2015. The use of this prophylaxis induced an effective GVHD prevention. However, infectious diseases were the most prevalent complication derived from the use of this approach (Salas et al. BMT, 2019).

Based on these results, the ATG dose was lowered to 2mg/kg (PTCY-ATG(2)-CsA) in 2018. The use of this refined combination resulting on a comparable effectivenes on GVHD prevention and less infectious complications (Salas et al. Eur. J. Hematology 2021).

The present análisis aims to compare the results provided by using PTCY-ATG(2)-CsA with those obtained using PTCY-ATG(4.5)-CsA and the previous Institutional GVHD prophylaxis used for 10/10 MUD PB allo-HCT which was composed by 4.5mg/kg of ATG combined with mycophenolate mofetil (MMF) and CsA (ATG-MMF-CsA).

METHODS Between 2011 and 2021, 444 patients underwent first PB allo-HCT from 10/10 MUD at our Institution and were included in the study. The study cohort was dividied into 2 groups: 84 adults that received ATG-based prophyaxis, 127 that received PTCY-ATG(4.5)-CsA and 233 received PTCY-ATG(2)-CsA. All patients received PB stem cell grafts from 10/10 MUD.

RESULTS Baseline charateristics are summarized in Table 1. As reported, the proportion of patients older tan 60 years was higher in patients receiving PTCY-ATG(2)-CSA than in the other 2 groups. Moreover, the proportions of patients with an HCT-CI score >3 and a high/very-high disease risk index were lower in this group of patients.

As shown in Figure 1, the cumulative incidence functions (CIF) of grade II-IV acute GVHD, grade III-IV acute GVHD at day 100, and moderate/severe chronic GVHD at 1 year were: 23.3%, 8.0% and 14.1% in patients receiving PTCY-ATG(2)-CsA, 16.5%, 4.9%, and 5.4% in patients receiving PTCYATG(4.5)-CSA, and 35.7%, 21.6%, and 14.7% in those receiving ATG-based prophylaxis.

Lastly, as reported in Figure 1, the estimated 1-year OS, RFS, GRFS, NRM and CIR were 78.3%, 69.2%, 56.2%, 14.7% and 16.1% for patients receiving PTCY-ATG(2)-CsA, 72.4%, 66.1%, 53.5%, 17.3%, and 16.5% for patients receiving PTCY-ATG(4.5)-CsA, and 68.6% (P=0.443), 66.3% (P=0.573), 43.0% (P=0.448), 25.3% (P=0.100), and 8.4% (P=0.243) for patients receiving ATG-based prophylaxis.

CONCLUSION The use of ATG-PTCY-CsA provides an effective prevention of acute and chronic GVHD, aceptable relapse rates, and results on a high overall survival.

Compared with using ATG-MMF-CSA, the use of this prophylaxis decreased rates of acute GVHD. Moreover using PTCY-ATG(4.5)-CsA decreased the proportion of moderate/severe cGVHD to only 8%.

Lastly, a trend to higher 1-year OS was documented in patients receiving PTCY-ATG(2)-CsA than in the rest ( 78.3% vs. 72.6% and 68.6%).

Law:Incyte Corporation: Research Funding; Kite Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Atara: Research Funding; Jazz Educational: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra: Research Funding. Kim:Paladin: Consultancy, Honoraria, Research Funding; Merck: Consultancy; Sanofi: Consultancy, Honoraria; BMS: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.