Pivotal studies using PTCY for GVHD prophylaxis
| Study . | Population . | Design . | Comparison . | Summary findings . |
|---|---|---|---|---|
| Haploidentical | ||||
| Luznik et al. (2008)20 | 0.5-70 years old receiving NMA BM HCT with haplo donors for hematologic disorders (n = 68) | Single-arm prospective multicenter | Single Arm PTCY/MMF/TAC | The CI of grades II-IV and III-IV acute GVHD by day +200 was 34% and 6%, respectively. Graft failure rate was 13%. CI of NRM and relapse at 1 year post-HCT was 15% and 51%, respectively. |
| Ciurea et al. (2015)21 | Adults with de novo or secondary AML who received their first HCT | Retrospective registry study | Haplo BM graft with PTCY prophylaxis (n = 192) vs PBSC mobilized or BMT graft 8/8 HLA-matched MUD receiving calcineurin inhibitor GVHD backbone (n = 1982) | CI of acute grades II-IV (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) was lower after haplo vs MUD in patients who received MAC. Similarly, CI of acute grades II-IV GVHD was 19% vs 28% (P = .05) and 34% vs 52% (P = .002) for chronic GVHD for RIC. OS was similar for haplo and MUD. |
| Fuchs et al. (2021)22 | Adults aged 18-70 (n = 368) with lymphoma or acute leukemia receiving RIC with Flu/Cy/TBI | Two parallel phase 2 trials | Umbilical cord blood (n = 186) with GVHD prophylaxis with cyclosporine and MMF vs haplo (n = 182) with GVHD prophylaxis with PTCY/TAC/MMF | Two-year PFS was 35% (95% CI, 28%-42%) vs 41% (95% CI, 34%-48%) after UCB compared to haplo, respectively (P = .41). Two-year NRM was significantly higher for UCB at 18% (95% CI, 13%-24%) vs 11% (95% CI, 6%-16%) or haplo, P = .04. Two-year OS after UCB was lower at 46% (95% CI, 38%-53%) vs 57% (95% CI, 49%- 64%) for haplo, respectively (P = .04). |
| Related/unrelated | ||||
| Bolaños-Meade et al. (2019)2 | 18-75 years old RIC HCT with related and MUD donors | Randomized phase 2 | TAC/MMF/PTCY (n = 92) or TAC/MTX/bortezomib (n = 89) or TAC/MTX/ maraviroc (n = 92) vs TAC/MTX (n = 224 controls) | PTCY/TAC/MMF had the best GRFS benefit with an HR of 0.72 (90% CI, 0.54-0.94, P = .044) compared to TAC/MTX. Results from this study prompted launch of phase 3 BMT CTN 1703 comparison of PTCY with MTX and calcineurin inhibitor for GVHD prophylaxis. |
| Luznik et al. (2022)26 | ≤65 receiving 8/8 HLA-matched MAC HCT for AML in CR or MDS with <5% blasts | Randomized phase 3 | (1) Ex vivo CD34 selected T-cell–depleted PBSC graft (n = 114), (2) unmanipulated BM graft followed by single-agent Cy (n = 114), and (3) TAC/MTX (n = 118) | Intent-to-treat 2-year CRFS was 50.6% for CD34 selection (HR in comparison to TAC/MTX, 0.80; 95% CI, 0.56-1.15; P = .24), 48.1% for PTCY (HR, 0.86; 0.61-1.23; P = .41), and 41.0% for control. Calcineurin-free regimens did not translate to improved survival. |
| Bolaños-Meade et al. (2022)25 | ≥18 with hematologic malignancies receiving RIC using a 6/6 MRD, (n = 128), 8/8 MUD (n = 288), or 7/8 single mismatched (n = 15) PBSC donor | Randomized phase 3 | TAC/MMF/PTCY (n = 214) vs TAC/MTX (n = 217) | The PTCY group had significantly lower hazard GRFS than TAC/MTX arm (HR, 0.641; 95% CI, 0.492-0.835; P = .001). Day 100 grade III-IV acute GVHD was 6.3% vs 14.7% (P = .001), and chronic GVHD rate at 1 year was 21.9% vs 35.1% (P = .005) for PTCY vs TAC/MTX, respectively. No difference in risk of relapse 1-year post-HCT (20.8% vs 20.2%, P = .9) was noted. |
| MMUD | ||||
| Malki et al. (2021)29 | Adults ≤75 years old receiving PBSC MMUD HCT using RIC or MAC with MMUD HLA matched ≥6/8 (N = 38) | Single-arm prospective | None. Single-arm PTCY/MMF/TAC | One-year OS and GRFS were 87% (95% CI, 71%-94%) and 68% (95% CI, 51%-81%), respectively. CI of NRM at 100 days and 1 year was 0% and 11% (95% CI, 4%-27%), respectively. CI 100-day acute GVHD grades II-IV and III-IV and 1-year chronic GVHD were 50% (95% CI, 36%-69%), 18% (95% CI, 9%-36%), and 48% (95% CI, 34%-68%), respectively. |
| Shaw et al. (2021)30 | 15-71 with hematologic malignancies using a BM graft with either MAC or RIC, mismatched in at least at least 1 allele (4-6/8) (N = 80) | Prospective phase 2 | PTCY/MMF/sirolimus vs CIBMTR contemporary controls with PTCY | Nearly 50% enrollment of ethnic minorities. The 1-year OS of 76% (90% CI, 67.3%-83.3%) was for all patients in the cohort and 72% and 79% for MAC and RIC, respectively. In regard to GVHD, patients receiving MAC had grade III-IV acute and chronic GVHD of 18% and 36% at 1 year, respectively. For RIC, no grade III-IV acute GVHD was noted with 18% chronic GVHD at 1 year. |
| Study . | Population . | Design . | Comparison . | Summary findings . |
|---|---|---|---|---|
| Haploidentical | ||||
| Luznik et al. (2008)20 | 0.5-70 years old receiving NMA BM HCT with haplo donors for hematologic disorders (n = 68) | Single-arm prospective multicenter | Single Arm PTCY/MMF/TAC | The CI of grades II-IV and III-IV acute GVHD by day +200 was 34% and 6%, respectively. Graft failure rate was 13%. CI of NRM and relapse at 1 year post-HCT was 15% and 51%, respectively. |
| Ciurea et al. (2015)21 | Adults with de novo or secondary AML who received their first HCT | Retrospective registry study | Haplo BM graft with PTCY prophylaxis (n = 192) vs PBSC mobilized or BMT graft 8/8 HLA-matched MUD receiving calcineurin inhibitor GVHD backbone (n = 1982) | CI of acute grades II-IV (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) was lower after haplo vs MUD in patients who received MAC. Similarly, CI of acute grades II-IV GVHD was 19% vs 28% (P = .05) and 34% vs 52% (P = .002) for chronic GVHD for RIC. OS was similar for haplo and MUD. |
| Fuchs et al. (2021)22 | Adults aged 18-70 (n = 368) with lymphoma or acute leukemia receiving RIC with Flu/Cy/TBI | Two parallel phase 2 trials | Umbilical cord blood (n = 186) with GVHD prophylaxis with cyclosporine and MMF vs haplo (n = 182) with GVHD prophylaxis with PTCY/TAC/MMF | Two-year PFS was 35% (95% CI, 28%-42%) vs 41% (95% CI, 34%-48%) after UCB compared to haplo, respectively (P = .41). Two-year NRM was significantly higher for UCB at 18% (95% CI, 13%-24%) vs 11% (95% CI, 6%-16%) or haplo, P = .04. Two-year OS after UCB was lower at 46% (95% CI, 38%-53%) vs 57% (95% CI, 49%- 64%) for haplo, respectively (P = .04). |
| Related/unrelated | ||||
| Bolaños-Meade et al. (2019)2 | 18-75 years old RIC HCT with related and MUD donors | Randomized phase 2 | TAC/MMF/PTCY (n = 92) or TAC/MTX/bortezomib (n = 89) or TAC/MTX/ maraviroc (n = 92) vs TAC/MTX (n = 224 controls) | PTCY/TAC/MMF had the best GRFS benefit with an HR of 0.72 (90% CI, 0.54-0.94, P = .044) compared to TAC/MTX. Results from this study prompted launch of phase 3 BMT CTN 1703 comparison of PTCY with MTX and calcineurin inhibitor for GVHD prophylaxis. |
| Luznik et al. (2022)26 | ≤65 receiving 8/8 HLA-matched MAC HCT for AML in CR or MDS with <5% blasts | Randomized phase 3 | (1) Ex vivo CD34 selected T-cell–depleted PBSC graft (n = 114), (2) unmanipulated BM graft followed by single-agent Cy (n = 114), and (3) TAC/MTX (n = 118) | Intent-to-treat 2-year CRFS was 50.6% for CD34 selection (HR in comparison to TAC/MTX, 0.80; 95% CI, 0.56-1.15; P = .24), 48.1% for PTCY (HR, 0.86; 0.61-1.23; P = .41), and 41.0% for control. Calcineurin-free regimens did not translate to improved survival. |
| Bolaños-Meade et al. (2022)25 | ≥18 with hematologic malignancies receiving RIC using a 6/6 MRD, (n = 128), 8/8 MUD (n = 288), or 7/8 single mismatched (n = 15) PBSC donor | Randomized phase 3 | TAC/MMF/PTCY (n = 214) vs TAC/MTX (n = 217) | The PTCY group had significantly lower hazard GRFS than TAC/MTX arm (HR, 0.641; 95% CI, 0.492-0.835; P = .001). Day 100 grade III-IV acute GVHD was 6.3% vs 14.7% (P = .001), and chronic GVHD rate at 1 year was 21.9% vs 35.1% (P = .005) for PTCY vs TAC/MTX, respectively. No difference in risk of relapse 1-year post-HCT (20.8% vs 20.2%, P = .9) was noted. |
| MMUD | ||||
| Malki et al. (2021)29 | Adults ≤75 years old receiving PBSC MMUD HCT using RIC or MAC with MMUD HLA matched ≥6/8 (N = 38) | Single-arm prospective | None. Single-arm PTCY/MMF/TAC | One-year OS and GRFS were 87% (95% CI, 71%-94%) and 68% (95% CI, 51%-81%), respectively. CI of NRM at 100 days and 1 year was 0% and 11% (95% CI, 4%-27%), respectively. CI 100-day acute GVHD grades II-IV and III-IV and 1-year chronic GVHD were 50% (95% CI, 36%-69%), 18% (95% CI, 9%-36%), and 48% (95% CI, 34%-68%), respectively. |
| Shaw et al. (2021)30 | 15-71 with hematologic malignancies using a BM graft with either MAC or RIC, mismatched in at least at least 1 allele (4-6/8) (N = 80) | Prospective phase 2 | PTCY/MMF/sirolimus vs CIBMTR contemporary controls with PTCY | Nearly 50% enrollment of ethnic minorities. The 1-year OS of 76% (90% CI, 67.3%-83.3%) was for all patients in the cohort and 72% and 79% for MAC and RIC, respectively. In regard to GVHD, patients receiving MAC had grade III-IV acute and chronic GVHD of 18% and 36% at 1 year, respectively. For RIC, no grade III-IV acute GVHD was noted with 18% chronic GVHD at 1 year. |
BM, bone marrow; CI, cumulative incidence; CIBMTR, Center for International Blood and Marrow Transplant Research; CR, complete remission; CRFS, chronic relapse-free survival; Cy, cyclophosphamide; Flu, fludarabine; MMUD, mismatched unrelated donor; MRD, matched related donor; MUD, matched unrelated donor; NMA, nonmyeloablative; PFS, progression-free survival; TBI, total body irradiation; UCB, umbilical cord blood.