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Lower GVHD and relapse risk in PTCy-based Haploidentical vs Matched Sibling Donor RIC Transplant for Hodgkin Lymphoma
Ahmed, S., Kanakry, J. A., Ahn, K. W., Litovich, C., Abdel-Azim, H., Aljurf, M., Bacher, V. U., Bejanyan, N., Cohen, J. B., Farooq, U., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Abstract
Classical Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of two reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with post-transplantation cyclophosphamide (PTCy)-based approach versus MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008-2016, using either haplo-PTCy (n=139) or MSD/CNI-based (n=457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute (a) and (c) graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR]=1.07; 95%CI=0.79-1.45; p=0.66) or PFS (HR=0.86; 95%CI=0.68-1.10; p=0.22). Haplo/PTCy was associated with a significantly higher risk of grade 2-4 aGVHD (odds ratio [OR]=1.73, 95%CI=1.16-2.59, p=0.007), but the risk of grade 3-4 aGVHD was not significantly different between the two cohorts (OR=0.61, 95%CI=0.29-1.27, p=0.19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR=0.45, 95%CI=0.32-0.64, p<0.001), and a significant reduction in relapse risk (HR=0.74, 95%CI=0.56-0.97, p=0.03). There was a statistically non-significant trend towards higher NRM with haplo/PTCy approach (HR=1.65, 95%CI=0.99-2.77, p=0.06). Haplo/PTCy-based approaches are associated with lower incidence of cGVHD and relapse, with PFS and OS outcomes comparable to MSD/CNI-based approaches. There was a leaning towards higher NRM with haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable to MSD/CNI-based allo-HCT.
PICO Summary
Population
Adult patients who underwent a first RIC allo-HCT for classical Hodgkin lymphoma between 2008-2016 (n=596)
Intervention
T cell-replete related donor haploidentical HCT with post-transplantation cyclophosphamide (Haplo/PTCy) (n=139)
Comparison
Matched Sibling Donor with calcineurin inhibitor (MSD/CNI) (n=457)
Outcome
On multivariate analysis, there was no significant difference between Haplo/PTCy and MSD/CNI-based approaches in terms of overall survival or progression-free survival. Haplo/PTCy was associated with a significantly higher risk of grade 2-4 aGVHD, but the risk of grade 3-4 aGVHD was not significantly different between the two cohorts. The haplo/PTCy platform provided a significant reduction in cGVHD risk, and a significant reduction in relapse. There was a statistically non-significant trend towards higher NRM with haplo/PTCy approach.