Representative GvHD prophylaxis trials using posttransplant cyclophosphamide, abatacept, and ATG in unrelated donor transplantation
| Trial/Reference . | Study design . | GvHD prophylaxis . | Acute GvHD . | Chronic GvHD . | Relapse . | Graft failure . | Survival . |
|---|---|---|---|---|---|---|---|
| Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD (ABA2) Ref.16 | Phase: 2 N: MUD (142), MMUD (43) Recipient Age: >6 years Donor: MUD, MMUD Graft Source: PBSC, BM Conditioning: MAC or RIC | CNI/MTX Randomized ± abatacept (MUD) CNI/MTX/ abatacept (MMUD) | MUD Grade 2-4: 43% Grade 3-4: 7% MUD Control Grade 2-4: 62% Grade 3-4: 15% MMUD Grade 2-4: 40% Grade 3-4: 2% | MUD Mild-Sev: 52% Mod-Sev: 45%, MUD control Mild-Sev: 45% Mod-Sev: 36% MMUD Mild-Sev: 22% Mod-Sev: 58% | 2-y Relapse: MUD 22% MMUD 9% MUD control 24% | Secondary graft failure N = 1 (MUD) | MUD 2-y NRM: 13% 2-y EFS: 66% 2-y OS: 74% MUD control 2-y NRM: 16% 2-y EFS: 60% 2-y OS: 64% MMUD 2-y NRM: 17% 2-y EFS: 74% 2-y OS: 74% |
| Addition of Anti-Thymocyte Globulin to Standard Graft-Versus-Host Disease prophylaxis Versus Standard Treatment Alone in Patients With Haematological Malignancies Undergoing Transplantation From Unrelated Donors: Final Analysis of a Randomized, Open-Label, Multicentre, Phase 3 Trial Ref.33 | Phase: 3 N: 203 Recipient Age: 16-70 y Donor: MUD, MMUD Graft Source: PBSC, BM Conditioning: MAC or RIC | CNI/MTX Or CNI/MMF + Randomized ± ATG | ATG Grade 2-4: NA Grade 3-4: 28% Control Grade 2-4: NA Grade 3-4: 28% | ATG Mild-Sev: 26% Mod-Sev: NA Control Mild-Sev: 40% Mod-Sev: NA | 2-y Relapse: ATG 16% Control 18% | NA | ATG 2-y NRM: 21% 2-y EFS: NA 2-y OS: 71% Control 2-y NRM: 31% 2-y EFS: NA 2-y OS: 53% |
| Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis (CTN 1703) Ref.10 | Phase: 3 N: 431 Recipient Age: >18 y Donor: MSD, MUD, MMUD Graft Source: PBSC Conditioning: RIC | PTCy/Tac/MMF Or Tac/MTX | PTCy/Tac/MMF Grade 2-4: 54% Grade 3-4: 6% Tac/MTX Grade 2-4: 52% Grade 3-4: 15% | PTCy/Tac/MMF Mild-Sev: 22% Mod-Sev: NA Tac/MTX Mild-Sev: 35% Mod-Sev: NA | PTCy/Tac/MMF 1-y Relapse: 21% Tac/MTX 1-y Relapse: 20% | PTCy/Tac/MMF 3% Tac/MTX | PTCy/Tac/MMF 1-y NRM: 12% 1-y EFS: 67% 1-y OS: 77% Tac/MTX 1-y NRM: 17% 1-y EFS: 62% 1-y OS: 72% |
| National Marrow Donor Program-Sponsored Multicenter, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation Using Post-Transplant Cyclophosphamide (15-MMUD) Ref.15 | Phase: 2 N: 40 MAC, 40 RIC Recipient Age: 18-70 Donor: MMUD Graft Source: BM Conditioning: MAC or RIC | PTCy/Sirolimus/ MMF | Grade 2-4: 48% MAC, 35% RIC Grade 3-4: 20% MAC, 3% RIC | Mild-Sev: 36% MAC, 18% RIC Mod-Sev: NA | 1-y Relapse: 30% MAC, 23% RIC | 0% MAC, 8% RIC | 1-y NRM: 8% MAC, 10% RIC 1-y EFS: 62% MAC, 68% RIC 1-y OS: 72% MAC, 79% RIC |
| Three Prophylaxis Regimens (Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide; Tacrolimus, Methotrexate, and Bortezomib; or Tacrolimus, Methotrexate, and Maraviroc) Versus Tacrolimus and Methotrexate for Prevention of Graft-Versus-Host Disease With Haemopoietic Cell Transplantation With Reduced-Intensity Conditioning: A Randomised Phase 2 Trial With a Non-Randomised Contemporaneous Control Group (BMT CTN 1203) Ref.9 | Phase: 2 N: 273 (92 PTCy) Recipient Age: 18-75 y Donor: MSD, MUD, MMUD Graft Source: PBSC Conditioning: RIC | PTCy/Tac/MMF Or Tac/MTX/ Bortezomib Or Tac/MTX/ maraviroc | PTCy/Tac/MMF Grade 2-4: 27% Grade 3-4:2% Tac/MTX Grade 2-4: 30% Grade 3-4: 13% | PTCy/Tac/MMF Mild-Sev: 28% Mod-Sev: NA Tac/MTX Mild-Sev: 38% Mod-Sev: NA | PTCy/Tac/MMF 1-y Relapse: 28% Tac/MTX 1-y Relapse: 25% | PTCy/Tac/MMF 4% Tac/MTX 0 | PTCy/Tac/MMF 1-y NRM: 11% 1-y EFS: 60% 1-y OS: 71% Tac/MTX 1-y NRM: 16% 1-y EFS: 56% 1-y OS: 71% |
| Randomized Phase 3 BMT CTN Trial of Calcineurin Inhibitor–Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies (CTN 1301) Ref.13 | Phase: 3 N: 346 Recipient Age: <65 y Donor: MSD, MUD Graft Source: BM, PBSC (CD34+ selection) Conditioning: MAC | Tac/MTX or PTCy Or none (CD34+ selection) | Tax/MTX Grade 2-4: 30% Grade 3-4:4% PTCy Grade 2-4: 38% Grade 3-4: 10% CD34+ selection Grade 2-4: 16% Grade 3-4: 3% | Tax/MTX Mild-Sev: NA Mod-Sev: 34% PTCy Mild-Sev: NA Mod-Sev: 27% CD34+ selection Mild-Sev: NA Mod-Sev: 9% | Tax/MTX 2-y Relapse: 26% PTCy 2-y Relapse: 14% CD34+ selection 2-y Relapse: 21% | Secondary graft failure Tax/MTX 1% PTCy 0% CD34+ selection 3% | Tax/MTX 2-y NRM: 8% 2-y EFS: 67% 2-y OS: 76% PTCy 2-y NRM: 16% 2-y EFS: 70% 2-y OS: 76% CD34+ selection 2-y NRM: 22% 1-y EFS: 57% 2-y OS: 60% |
| Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation With Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil Ref.14 | Phase 2 N: 125 Recipient Age: median 39 y Donor: MUD, MMUD Graft Source: BM, PBSC Conditioning: MAC | PTCy/Tac/MMF | Grade 2-4: 17% Grade 3-4: 6% | Mild-Sev: NA Requiring IST: 6% | 2-y Relapse: 39% | NA | 2-y NRM: 10% 2-y EFS: 2-y OS: 74% |
| Trial/Reference . | Study design . | GvHD prophylaxis . | Acute GvHD . | Chronic GvHD . | Relapse . | Graft failure . | Survival . |
|---|---|---|---|---|---|---|---|
| Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD (ABA2) Ref.16 | Phase: 2 N: MUD (142), MMUD (43) Recipient Age: >6 years Donor: MUD, MMUD Graft Source: PBSC, BM Conditioning: MAC or RIC | CNI/MTX Randomized ± abatacept (MUD) CNI/MTX/ abatacept (MMUD) | MUD Grade 2-4: 43% Grade 3-4: 7% MUD Control Grade 2-4: 62% Grade 3-4: 15% MMUD Grade 2-4: 40% Grade 3-4: 2% | MUD Mild-Sev: 52% Mod-Sev: 45%, MUD control Mild-Sev: 45% Mod-Sev: 36% MMUD Mild-Sev: 22% Mod-Sev: 58% | 2-y Relapse: MUD 22% MMUD 9% MUD control 24% | Secondary graft failure N = 1 (MUD) | MUD 2-y NRM: 13% 2-y EFS: 66% 2-y OS: 74% MUD control 2-y NRM: 16% 2-y EFS: 60% 2-y OS: 64% MMUD 2-y NRM: 17% 2-y EFS: 74% 2-y OS: 74% |
| Addition of Anti-Thymocyte Globulin to Standard Graft-Versus-Host Disease prophylaxis Versus Standard Treatment Alone in Patients With Haematological Malignancies Undergoing Transplantation From Unrelated Donors: Final Analysis of a Randomized, Open-Label, Multicentre, Phase 3 Trial Ref.33 | Phase: 3 N: 203 Recipient Age: 16-70 y Donor: MUD, MMUD Graft Source: PBSC, BM Conditioning: MAC or RIC | CNI/MTX Or CNI/MMF + Randomized ± ATG | ATG Grade 2-4: NA Grade 3-4: 28% Control Grade 2-4: NA Grade 3-4: 28% | ATG Mild-Sev: 26% Mod-Sev: NA Control Mild-Sev: 40% Mod-Sev: NA | 2-y Relapse: ATG 16% Control 18% | NA | ATG 2-y NRM: 21% 2-y EFS: NA 2-y OS: 71% Control 2-y NRM: 31% 2-y EFS: NA 2-y OS: 53% |
| Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis (CTN 1703) Ref.10 | Phase: 3 N: 431 Recipient Age: >18 y Donor: MSD, MUD, MMUD Graft Source: PBSC Conditioning: RIC | PTCy/Tac/MMF Or Tac/MTX | PTCy/Tac/MMF Grade 2-4: 54% Grade 3-4: 6% Tac/MTX Grade 2-4: 52% Grade 3-4: 15% | PTCy/Tac/MMF Mild-Sev: 22% Mod-Sev: NA Tac/MTX Mild-Sev: 35% Mod-Sev: NA | PTCy/Tac/MMF 1-y Relapse: 21% Tac/MTX 1-y Relapse: 20% | PTCy/Tac/MMF 3% Tac/MTX | PTCy/Tac/MMF 1-y NRM: 12% 1-y EFS: 67% 1-y OS: 77% Tac/MTX 1-y NRM: 17% 1-y EFS: 62% 1-y OS: 72% |
| National Marrow Donor Program-Sponsored Multicenter, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation Using Post-Transplant Cyclophosphamide (15-MMUD) Ref.15 | Phase: 2 N: 40 MAC, 40 RIC Recipient Age: 18-70 Donor: MMUD Graft Source: BM Conditioning: MAC or RIC | PTCy/Sirolimus/ MMF | Grade 2-4: 48% MAC, 35% RIC Grade 3-4: 20% MAC, 3% RIC | Mild-Sev: 36% MAC, 18% RIC Mod-Sev: NA | 1-y Relapse: 30% MAC, 23% RIC | 0% MAC, 8% RIC | 1-y NRM: 8% MAC, 10% RIC 1-y EFS: 62% MAC, 68% RIC 1-y OS: 72% MAC, 79% RIC |
| Three Prophylaxis Regimens (Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide; Tacrolimus, Methotrexate, and Bortezomib; or Tacrolimus, Methotrexate, and Maraviroc) Versus Tacrolimus and Methotrexate for Prevention of Graft-Versus-Host Disease With Haemopoietic Cell Transplantation With Reduced-Intensity Conditioning: A Randomised Phase 2 Trial With a Non-Randomised Contemporaneous Control Group (BMT CTN 1203) Ref.9 | Phase: 2 N: 273 (92 PTCy) Recipient Age: 18-75 y Donor: MSD, MUD, MMUD Graft Source: PBSC Conditioning: RIC | PTCy/Tac/MMF Or Tac/MTX/ Bortezomib Or Tac/MTX/ maraviroc | PTCy/Tac/MMF Grade 2-4: 27% Grade 3-4:2% Tac/MTX Grade 2-4: 30% Grade 3-4: 13% | PTCy/Tac/MMF Mild-Sev: 28% Mod-Sev: NA Tac/MTX Mild-Sev: 38% Mod-Sev: NA | PTCy/Tac/MMF 1-y Relapse: 28% Tac/MTX 1-y Relapse: 25% | PTCy/Tac/MMF 4% Tac/MTX 0 | PTCy/Tac/MMF 1-y NRM: 11% 1-y EFS: 60% 1-y OS: 71% Tac/MTX 1-y NRM: 16% 1-y EFS: 56% 1-y OS: 71% |
| Randomized Phase 3 BMT CTN Trial of Calcineurin Inhibitor–Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies (CTN 1301) Ref.13 | Phase: 3 N: 346 Recipient Age: <65 y Donor: MSD, MUD Graft Source: BM, PBSC (CD34+ selection) Conditioning: MAC | Tac/MTX or PTCy Or none (CD34+ selection) | Tax/MTX Grade 2-4: 30% Grade 3-4:4% PTCy Grade 2-4: 38% Grade 3-4: 10% CD34+ selection Grade 2-4: 16% Grade 3-4: 3% | Tax/MTX Mild-Sev: NA Mod-Sev: 34% PTCy Mild-Sev: NA Mod-Sev: 27% CD34+ selection Mild-Sev: NA Mod-Sev: 9% | Tax/MTX 2-y Relapse: 26% PTCy 2-y Relapse: 14% CD34+ selection 2-y Relapse: 21% | Secondary graft failure Tax/MTX 1% PTCy 0% CD34+ selection 3% | Tax/MTX 2-y NRM: 8% 2-y EFS: 67% 2-y OS: 76% PTCy 2-y NRM: 16% 2-y EFS: 70% 2-y OS: 76% CD34+ selection 2-y NRM: 22% 1-y EFS: 57% 2-y OS: 60% |
| Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation With Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil Ref.14 | Phase 2 N: 125 Recipient Age: median 39 y Donor: MUD, MMUD Graft Source: BM, PBSC Conditioning: MAC | PTCy/Tac/MMF | Grade 2-4: 17% Grade 3-4: 6% | Mild-Sev: NA Requiring IST: 6% | 2-y Relapse: 39% | NA | 2-y NRM: 10% 2-y EFS: 2-y OS: 74% |
BM, bone marrow; CNI, calcineurin inhibitor; EFS, event-free survival; IST, immunosuppressive treatment; Mod, moderate; MSD, matched sibling donor; NA, not available; NRM, nonrelapse mortality; OS, overall survival; Sev, severe.