HL

Results from a EBMT registry study in Hodgkin Lymphoma: HAPLO comparability to SIB and MUD confirms its suitability for advanced HL when lacking a conventional donor

On October 20, 2017, Carmen Martinez of the Institute of Hematology and Oncology in Barcelona, Spain and colleagues published in The Journal of Clinical Oncology a retrospective analysis of 709 adult patients with Hodgkin lymphoma (HL). This study included patients who were registered in the European Society for Blood and Marrow Transplantation (EBMT) database who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation, conventional HLA-matched sibling donor (SIB), or HLA matched unrelated donor (MUD). The objective of this study was to compare the outcome of patients with HL who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation.

Key Highlights:
  • Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD
  • Results support use of HAPLO as an alternative for patients with advanced HL who lack an SIB donor
  • HAPLO donors may allow patients to proceed more rapidly to transplantation
Treatment:
  • 709 adult patients aged > 18 years who had undergone alloHCT for HL between January 2010 and December 2013
    • Transplantations from mismatched related donors—two or more mismatches—were identified as HAPLO transplantations
Results:
  • No differences were observed between groups in the incidence of acute graft-versus-host disease (GvHD)
  • HAPLO was associated with a lower risk of chronic GvHD (26%) compared with MUD (41%; P = 0.04)
  • Cumulative incidence of non-relapse mortality at 1 year:
    • HAPLO: 17%
    • SIB: 13%
    • MUD: 21%
  • Corresponding 2-year cumulative incidence of relapse or progression: was 39%, 49%, and 32%,
    • HAPLO: 39%
    • SIB: 49%
    • MUD: 32%
  • Relative to SIB, non-relapse mortality (NRM) was similar in HAPLO (P = 0.26) and higher in MUD (P = 0.003), and risk of relapse was lower in both HAPLO (P = 0.047) and MUD (P < 0.001)
  • There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD
    • Two-year overall survival (OS):
      • HAPLO: 67%
      • SIB: 71%
      • MUD: 62%
    • Two-year progression-free survival (PFS):
      • HAPLO: 43%
      • SIB: 38%
      • MUD: 45%

Per current recommendations of the EBMT, alloHCT is considered the standard treatment option in eligible patients who experience sensitive relapse after autologous hematopoietic cell transplantation and with a SIB or a MUD donor; however, there is a significant proportion of patients for whom a conventional donor is not available. This retrospective study of 709 adult HL patients demonstrated that post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes when compared to those that employed SIB and MUD. The results also suggested that HAPLO results in a lower risk of chronic GvHD than MUD transplantation. The study authors concluded that only a randomized prospective clinical trial can determine whether HAPLO transplantation ought to be first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients. This study provides compelling evidence that HAPLO is a viable choice in adult HL patients when no conventional donor is available.

Abstract

Purpose: To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide–based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods: We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results: Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO (P = .26) and higher in MUD (P = .003), and risk of relapse was lower in both HAPLO (P = .047) and MUD (P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite endpoint of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion: Post-transplantation cyclophosphamide–based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.

References
  1. Martinez C. Et al. Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation. Journal of Clinical Oncology. 2017 Oct 20. DOI: https://doi.org/10.1200/JCO.2017.72.6869. Epub 2017 Aug 28