Introduction: Autologous hematopoietic stem cell transplantation (auto-HSCT) remains a standard of care for patients with chemosensitive relapsed/refractory Hodgkin lymphoma (HL) and allogeneic transplant (allo-HSCT) for patients who failed a prior auto-HSCT. Brentuximab vedotin (BV) and checkpoint inhibitors (CPI) have changed the landscape of HL treatment.

Methods: Using the European Society for Blood and Marrow Transplantation (EBMT) registry, we assessed changes over time in 15,648 patients who received an auto-HSCT and 3850 an allo-HSCT between 2010 and 2022.

Results: For auto-SCT, when comparing three periods (2010-2014 N = 6,896; 2015-2018 N = 4,739; and 2019-2022 N = 4,013), patients transplanted in recent years were older, more likely to have received BV and/or CPI pretransplant, and more frequently transplanted in complete remission (CR) and PET scan negativity. The 2-year progression free survival (PFS) increased from 63% to 69% and 73% over the three time periods and the 2-year overall survival (OS) increased from 85% to 91% and 93% respectively. Improvement over time was noted in patients transplanted in partial response (PR) (2-year PFS 56%, 57% and 65%) whereas that of patients autografted in CR remained stable at 77%. In multivariate analysis (MVA), transplantation in recent years significantly improved PFS (HR 0.9, p=0.046 for 2015-2018; and 0.79, p<0.001 for 2019-2022, both compared to 2010-2014) and OS (HR 0.6, p<0.001 and 0.55, p<0.001). PFS and OS were positively affected by female gender (HR 0.89 and 0.83 respectively, p=0.009 for both), time from diagnosis to auto-HSCT > 24 months (HR 0.71, p<0.001; and 0.82, p=0.005) and Karnofsky score > 90 (HR 0.85, p=0.003; and 0.75, p<0.001). PFS and OS were negatively affected by transplantation in PR (HR 1.62 and 1.81 respectively, p<0.001 for both) or in refractory status (HR 2.45 and 2.56 respectively, p<0.001 for both) as well as HSCT comorbidity index > 3 (HR 1.57 and 1.33, p<0.001 for both). Older age negatively affected OS (HR for 5-years increase 1.15 p<0.001). For allo-SCT, when comparing the three periods (2010-2014 N = 1673; 2015-2018 N = 1229; and 2019-2022 N = 948), patients transplanted in recent years were older, had a longer time from diagnosis to transplant, more likely to have received BV and/or CPI pretransplant, more frequently transplanted in CR and PET negativity, more likely to have received transplant from mismatched relative (predominantly haplo-identical) donor (MMRD) and post-transplant cyclophosphamide (PTCy). The 2-year PFS increased from 44% to 58% and 62% over the three time periods and the 2-year OS went from 66% to 73% and 72% respectively. Importantly, the 2-year GVHD and relapse free survival (GRFS) increased from 32% to 43% and 50% respectively. In MVA, transplantation in recent years significantly improved PFS (HR 0.78, p<0.001 for 2015-2018; and 0.7 p<0.001; both compared to 2010-2014), OS (HR 0.8, p=0.001 and 0.84, p=0.049) and GRFS (HR 0.88, p=0.012 and 0.75, p<0.001). PFS and OS were negatively affected by older age (HR for 5-years increase 1.08 and 1.14, p<0.001 for both), transplantation in PR (HR 1.58 and 1.34, p<0.001 for both) or refractory disease (HR 2.28 and 2.1, p<0.001 for both). OS was also negatively affected by myeloablative conditioning (HR 1.22, p=0.002). Compared to matched related donor (MRD) without PTCY, OS was negatively affected by the use of MMRD without PTCy (HR 1.38, p=0.019), unrelated donor (UD) without PTCy (HR 1.29, p<0.001), or MMRD with PTCy (HR 1.21, p=0.031), but not significantly affected by other combinations, whereas PFS was positively affected by the use of UD with PTCy (HR 0.64, p=0.005) but not significantly affected by other combinations. In separate MVA starting from 2015, CPI use before allo-HSCT significantly improved PFS (HR 0.79, p=0.025) whereas BV use before allo-HSCT did not significantly affect PFS and OS.Conclusion: outcomes after auto-HSCT and allo-HSCT continue to improve over time. For auto-HSCT, transplantation in CR, younger age, female gender, Karnofsky > 90, low comorbidity index and a longer interval from diagnosis to HSCT significantly improve survival. For allo-HSCT, transplantation in CR, younger age, and reduced intensity conditioning significantly improve survival. CPI use before allo-HSCT significantly improved PFS. MRD is the preferred donor option in the absence of PTCy, whereas the combination of UD and PTCy yield the best outcomes.

This content is only available as a PDF.
2025
Sign in via your Institution