Contributions
Abstract: S233
Type: Oral Presentation
Session title: Stem cell transplantation - Preclinical/experimental
Background
GVHD prophylaxis may affect the transplant (HSCT) mediated graft-versus-leukemia (GVL) effect and post- HSCT relapse (RI). Pre-transplant measurable residual disease (MRD) predicts RI and outcome of HSCT with calcineurin based anti GVHD prophylaxis. Post-transplant cyclophosphamide (PTCy) has changed immune reconstitution post-transplant, upregulating T regulatory (Treg) cells while ablating recipient proliferating NK cells . It is therefore conceivable that MRD prediction of RI post-HSCT with PTCy will be different.
Aims
Study aim was to assess the prognostic impact of pre-HSCT MRD in adult patients (pts), aged ≥18 y with AML in CR undergoing HSCT from a 9-10/10 unrelated donor (MUD) with PTCy, in 2010-2019.
Methods
Multivariate analysis (MVA) adjusting for potential confounding factors was performed using a Cox’s proportional-hazards regression model for main outcomes .
Results In MRD- and MRD+ pts, engraftment was achieved by 97.4% and 97%, respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was 28.1% and 25.6% (p=0.67), and 8.2% and 12.3% (p=0.28), respectively, and 2-y total and extensive chronic (c) GVHD was 27.2% and 31.8 % (p=0.6), and 5.9% and 17.6 % (p=0.03). The 2-y NRM was 8.2% and 13.9% (p=0.32). The 2-y RI was significantly lower in MRD- vs MRD+ pts: 20.4% vs 32%, respectively (HR=1.87; 95% CI: 1.12-3.14; p=0.02)' ) and it was the main cause of death in 35.9% and 50% of pts who died. The 2-y LFS and GRFS was significantly better in MRD- vs MRD+ pts being 71.4% vs 51.4%, and 61.3% vs 40.2% (p=0.021 and p=0.01), respectively, while OS did not differ being 76.1% and 65.8%, respectively (p=0.2). These results were confirmed by MVA: RI was significantly lower while LFS and GRFS were significantly higher in MRD- vs MRD+ pts: hazard ratio (HR)=1.87 (95% CI 1.12-3.14, p<0.02), HR=1.59 (95% CI 1.02-2.45, p<0.04) and HR=1.69 (95% CI 1.16-2.47, p< 0.01), respectively. NRM and OS were similar between the groups: H=1.07 (95% CI 0.47-2.43, p=0.88) and HR=1.2 (95% CI 0.73-1.95, p=0.48), respectively. Risk of aGVHD II-IV and total cGVHD was also similar, HR=0.89 (95% CI 0.55-1.45, p=0.63), and HR=1.61 (95% CI 0.94-2.77, p=0.08), respectively.
290 pts were included: MRD- -189, MRD+ -101. Median F/U was 17.7 (13.8-23.8) and 21.6 (16.8-26.5) months (p=0.61). Median age was 46.7 (18-74) and 50 (18-72) y, (p=0.018) . 55% and 63.4% were male (p=0.77), 44.4% and 50.5% were classified as intermediate cytogenetic risk, while 15.3% and 18.8%, and 11.6% and 15.8% were classified as adverse and favorable risk cytogenetics, respectively (p=0.069). Pre-MUD disease status was CR1 in 76.2% and 80.2%, and CR2 in 23.8% and 19.8% of the pts, respectively ( p=0.44) . 45% and 43.1% of the pts harbored the FLT3+ mutation (p=0.83), (missing in ~50%). Conditioning was myeloablative in 64% and 59.4% (p=0.44). In vivo T-cell depletion was used in 28.6% and 18.8% of transplants (p=0.068). Graft was peripheral blood in 92.6% and 91.1% of transplants (p=0.65). Karnofsky performance score was > 90 in 80.6% and 75.5% of pts (p=0.31).
Conclusion
In AML pts undergoing HSCT from a 9-10/10 MUD in CR with PTCy as GVHD prophylaxis, pre-transplant MRD negativity predicted transplantation outcome correlating with lower relapse rate and better LFS and GRFS, similar to previous reports using conventional GVHD prophylaxis. These findings may indicate that PTCy does not jeopardize the transplant mediated GVL effect and the importance of the pre-HSCT remission depth, despite the PTCy mediated NK inhibitory and Treg cell potentiating activity leading to a lower incidence of cGVHD
Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, MRD, Relapse
Abstract: S233
Type: Oral Presentation
Session title: Stem cell transplantation - Preclinical/experimental
Background
GVHD prophylaxis may affect the transplant (HSCT) mediated graft-versus-leukemia (GVL) effect and post- HSCT relapse (RI). Pre-transplant measurable residual disease (MRD) predicts RI and outcome of HSCT with calcineurin based anti GVHD prophylaxis. Post-transplant cyclophosphamide (PTCy) has changed immune reconstitution post-transplant, upregulating T regulatory (Treg) cells while ablating recipient proliferating NK cells . It is therefore conceivable that MRD prediction of RI post-HSCT with PTCy will be different.
Aims
Study aim was to assess the prognostic impact of pre-HSCT MRD in adult patients (pts), aged ≥18 y with AML in CR undergoing HSCT from a 9-10/10 unrelated donor (MUD) with PTCy, in 2010-2019.
Methods
Multivariate analysis (MVA) adjusting for potential confounding factors was performed using a Cox’s proportional-hazards regression model for main outcomes .
Results In MRD- and MRD+ pts, engraftment was achieved by 97.4% and 97%, respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was 28.1% and 25.6% (p=0.67), and 8.2% and 12.3% (p=0.28), respectively, and 2-y total and extensive chronic (c) GVHD was 27.2% and 31.8 % (p=0.6), and 5.9% and 17.6 % (p=0.03). The 2-y NRM was 8.2% and 13.9% (p=0.32). The 2-y RI was significantly lower in MRD- vs MRD+ pts: 20.4% vs 32%, respectively (HR=1.87; 95% CI: 1.12-3.14; p=0.02)' ) and it was the main cause of death in 35.9% and 50% of pts who died. The 2-y LFS and GRFS was significantly better in MRD- vs MRD+ pts being 71.4% vs 51.4%, and 61.3% vs 40.2% (p=0.021 and p=0.01), respectively, while OS did not differ being 76.1% and 65.8%, respectively (p=0.2). These results were confirmed by MVA: RI was significantly lower while LFS and GRFS were significantly higher in MRD- vs MRD+ pts: hazard ratio (HR)=1.87 (95% CI 1.12-3.14, p<0.02), HR=1.59 (95% CI 1.02-2.45, p<0.04) and HR=1.69 (95% CI 1.16-2.47, p< 0.01), respectively. NRM and OS were similar between the groups: H=1.07 (95% CI 0.47-2.43, p=0.88) and HR=1.2 (95% CI 0.73-1.95, p=0.48), respectively. Risk of aGVHD II-IV and total cGVHD was also similar, HR=0.89 (95% CI 0.55-1.45, p=0.63), and HR=1.61 (95% CI 0.94-2.77, p=0.08), respectively.
290 pts were included: MRD- -189, MRD+ -101. Median F/U was 17.7 (13.8-23.8) and 21.6 (16.8-26.5) months (p=0.61). Median age was 46.7 (18-74) and 50 (18-72) y, (p=0.018) . 55% and 63.4% were male (p=0.77), 44.4% and 50.5% were classified as intermediate cytogenetic risk, while 15.3% and 18.8%, and 11.6% and 15.8% were classified as adverse and favorable risk cytogenetics, respectively (p=0.069). Pre-MUD disease status was CR1 in 76.2% and 80.2%, and CR2 in 23.8% and 19.8% of the pts, respectively ( p=0.44) . 45% and 43.1% of the pts harbored the FLT3+ mutation (p=0.83), (missing in ~50%). Conditioning was myeloablative in 64% and 59.4% (p=0.44). In vivo T-cell depletion was used in 28.6% and 18.8% of transplants (p=0.068). Graft was peripheral blood in 92.6% and 91.1% of transplants (p=0.65). Karnofsky performance score was > 90 in 80.6% and 75.5% of pts (p=0.31).
Conclusion
In AML pts undergoing HSCT from a 9-10/10 MUD in CR with PTCy as GVHD prophylaxis, pre-transplant MRD negativity predicted transplantation outcome correlating with lower relapse rate and better LFS and GRFS, similar to previous reports using conventional GVHD prophylaxis. These findings may indicate that PTCy does not jeopardize the transplant mediated GVL effect and the importance of the pre-HSCT remission depth, despite the PTCy mediated NK inhibitory and Treg cell potentiating activity leading to a lower incidence of cGVHD
Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, MRD, Relapse