Representative graft manipulation trials for GvHD prophylaxis in patients undergoing stem cell transplantation for hematologic malignancies
| Approach . | Study design . | GvHD prophylaxis . | Acute GvHD . | Chronic GvHD . | Relapse . | Graft failure . | Survival . |
|---|---|---|---|---|---|---|---|
| Tn-depleted PBSC + CD34+-selected PBSC Ref.25 | Phase: 2 N: 138 Recipient Age: 1-60 y Donor: MRD, MUD Conditioning: MAC | Tac Tac/MTX Tac/MMF | Grade 2: 71% Grade 3-4: 4% | Mild-Sev:6% Mod-Sev:1% | 3-y Relapse: 23% | Primary graft failure: 0 Secondary graft failure: N = 2 | 3-y NRM: 8% 3-y EFS: 69% 3-y OS: 77% |
| TCRab-depleted/ CD19-depleted PBSC Ref.27 | Phase: 2 N: 60 Recipient Age: >20 y Donor: Haplo Conditioning: MAC | CSA | Grade 2-4: 34% Grade 3-4: N = 18 | Mild-Sev: 25% Mod-Sev: N = 12 | Median follow-up 28 months Relapse 27% | Primary graft failure N = 4 | Median follow-up 28 months NRM: 23% EFS: 52% OS: NA |
| ORCA-T Manufactured cellular therapy with stem cells and Tregs Ref.31 | Phase: 1b, 2 N: 127 Recipient Age: 19-69 y Donor: MRD, MUD Conditioning: MAC | Tac or sirolimus | Grade 2-4: NA Grade 3-4: 5% | Mild-Sev: NA Mod-Sev: 6% | Relapse: NA | Primary graft failure 2% | 1-y NRM:5% 1.5-y EFS: 81% 1.5-y OS: 86% |
| CD34+-selected PBSC graft + Tn-depleted PBSC graft Ref.23 | Phase: NA N: 25 Recipient Age: 2-17 y Donor: Haplo Conditioning: MAC | CSA = 3 CSA/MTX = 1 MMF = 21 | Grade 2-4: 39% Grade 3-4: 33% | Mild-Sev: 22% Mod-Sev: N = 2 | 2.5-y Relapse: 17% | Primary graft failure: 0 Secondary graft failure: N = 2 | 2.5-y NRM: 22% EFS: NA 2.5-y OS: 58% |
| TCRab-depleted PBSC graft Ref.28 | Phase: 1/2 N: 35 Recipient Age: 19-69 y Donor: MRD, MUD, MMUD Conditioning: MAC | ATG MMF | Grade 2-4: 26% Grade 3-4: 14% | Mild-Sev: 23% Mod-Sev: 17% | 2-y Relapse: 29% | Primary graft failure: 0 Secondary graft failure: N = 1 | 2-y NRM: 32% 2-y EFS: 40% 2-y OS: 54% |
| TCRab-depleted/ CD19-depleted PBSC graft Ref. 22 | Phase: NA N: 60 Recipient Age: 1-23 y Donor: MUD, MMUD Conditioning: MAC | ATG = 22 | Grade 2-4: NA Grade 3-4: 13% | Mild-Sev: 26% Mod-Sev: NA (Extensive 11%) | Median follow-up 3.1 y Relapse: 21% | Primary graft failure: 1 | 3-y NRM: 15% 4-y EFS: 64% 4-y OS: 69% |
| TCRab-depleted/ CD19-depleted PBSC graft Ref.24 | Phase: 1/2 N: 60 Recipient Age: 1-63 y Donor: Haplo Conditioning: RIC | MMF ± ATG | Grade 2-4: 10% Grade 3-4: 0% | Mild-Sev: 31% Mod-Sev: 21% | 2-y Relapse: 21% | Primary graft failure: 9 | 2-y NRM: 17% 2-y EFS: 50% 2-y OS: 63% |
| Approach . | Study design . | GvHD prophylaxis . | Acute GvHD . | Chronic GvHD . | Relapse . | Graft failure . | Survival . |
|---|---|---|---|---|---|---|---|
| Tn-depleted PBSC + CD34+-selected PBSC Ref.25 | Phase: 2 N: 138 Recipient Age: 1-60 y Donor: MRD, MUD Conditioning: MAC | Tac Tac/MTX Tac/MMF | Grade 2: 71% Grade 3-4: 4% | Mild-Sev:6% Mod-Sev:1% | 3-y Relapse: 23% | Primary graft failure: 0 Secondary graft failure: N = 2 | 3-y NRM: 8% 3-y EFS: 69% 3-y OS: 77% |
| TCRab-depleted/ CD19-depleted PBSC Ref.27 | Phase: 2 N: 60 Recipient Age: >20 y Donor: Haplo Conditioning: MAC | CSA | Grade 2-4: 34% Grade 3-4: N = 18 | Mild-Sev: 25% Mod-Sev: N = 12 | Median follow-up 28 months Relapse 27% | Primary graft failure N = 4 | Median follow-up 28 months NRM: 23% EFS: 52% OS: NA |
| ORCA-T Manufactured cellular therapy with stem cells and Tregs Ref.31 | Phase: 1b, 2 N: 127 Recipient Age: 19-69 y Donor: MRD, MUD Conditioning: MAC | Tac or sirolimus | Grade 2-4: NA Grade 3-4: 5% | Mild-Sev: NA Mod-Sev: 6% | Relapse: NA | Primary graft failure 2% | 1-y NRM:5% 1.5-y EFS: 81% 1.5-y OS: 86% |
| CD34+-selected PBSC graft + Tn-depleted PBSC graft Ref.23 | Phase: NA N: 25 Recipient Age: 2-17 y Donor: Haplo Conditioning: MAC | CSA = 3 CSA/MTX = 1 MMF = 21 | Grade 2-4: 39% Grade 3-4: 33% | Mild-Sev: 22% Mod-Sev: N = 2 | 2.5-y Relapse: 17% | Primary graft failure: 0 Secondary graft failure: N = 2 | 2.5-y NRM: 22% EFS: NA 2.5-y OS: 58% |
| TCRab-depleted PBSC graft Ref.28 | Phase: 1/2 N: 35 Recipient Age: 19-69 y Donor: MRD, MUD, MMUD Conditioning: MAC | ATG MMF | Grade 2-4: 26% Grade 3-4: 14% | Mild-Sev: 23% Mod-Sev: 17% | 2-y Relapse: 29% | Primary graft failure: 0 Secondary graft failure: N = 1 | 2-y NRM: 32% 2-y EFS: 40% 2-y OS: 54% |
| TCRab-depleted/ CD19-depleted PBSC graft Ref. 22 | Phase: NA N: 60 Recipient Age: 1-23 y Donor: MUD, MMUD Conditioning: MAC | ATG = 22 | Grade 2-4: NA Grade 3-4: 13% | Mild-Sev: 26% Mod-Sev: NA (Extensive 11%) | Median follow-up 3.1 y Relapse: 21% | Primary graft failure: 1 | 3-y NRM: 15% 4-y EFS: 64% 4-y OS: 69% |
| TCRab-depleted/ CD19-depleted PBSC graft Ref.24 | Phase: 1/2 N: 60 Recipient Age: 1-63 y Donor: Haplo Conditioning: RIC | MMF ± ATG | Grade 2-4: 10% Grade 3-4: 0% | Mild-Sev: 31% Mod-Sev: 21% | 2-y Relapse: 21% | Primary graft failure: 9 | 2-y NRM: 17% 2-y EFS: 50% 2-y OS: 63% |
CSA, cyclosporine; haplo, haploidentical; Tn, naive T cells; TCRab, αβ + T cells; Tregs, regulatory T cells.