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Clinical Trial
. 2022 Jun 14;6(11):3378-3385.
doi: 10.1182/bloodadvances.2021005847.

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial

Annoek E C Broers  1 , Cornelis N de Jong  1   2 , Katerina Bakunina  3 , Mette D Hazenberg  4 , Marinus van Marwijk Kooy  5 , Marco R de Groot  6 , Michel van Gelder  7 , Jürgen Kuball  8 , Bronno van der Holt  3 , Ellen Meijer  9 , Jan J Cornelissen  1
Affiliations
Clinical Trial

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial

Annoek E C Broers et al. Blood Adv. .

Abstract

Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse-free survival (GRFS) as compared with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA-matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA; a total of 151 patients were transplanted (52 vs 99 patients, respectively). The cumulative incidence of grade 2 to 4 acute GVHD at 6 months was 48% in recipients of CsA/MPA vs 30% following PT-Cy/CsA (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.82; P = .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16% (HR, 0.36; 95% CI, 0.21-0.64; P < .001). The 1-year estimate of GRFS was 21% (11% to 32%) vs 45% (35% to 55%), P < .001. With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Acute and chronic GVHD. Cumulative incidence of grade 2-4 acute GVHD (A) and chronic extensive GVHD (B). GVHD denotes graft-versus-host disease, CsA cyclosporine A, MPA mycophenolic acid, and PT-Cy posttransplant cyclophosphamide.
Figure 2.
Figure 2.
Non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS). Cumulative incidence of NRM (A) and relapse/progression (B). Kaplan Meier estimates of PFS (C) and OS (D) CsA denotes cyclosporine A, MPA mycophenolic acid, and PT-Cy posttransplant cyclophosphamide.
Figure 3.
Figure 3.
GVHD free, relapse free survival (GRFS). Kaplan Meier estimate of GRFS (A) and forest plot of GRFS by donor type (B) GVHD denotes graft-versus-host disease, CsA cyclosporine A, MPA mycophenolic acid, and PT-Cy posttransplant cyclophosphamide.
See this image and copyright information in PMC

References

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