Evolution of Outcome over Time for Relapsed Hodgkin Lymphoma after Autologous Stem Cell Transplant: Improved Survival for Early Relapse in Recent Years

Salvage chemotherapy and autologous stem cell transplantation (auto-SCT) results in the cure of around 50% of patients with Hodgkin lymphoma (HL) failing first line therapy. In historical data, patients who progressed after auto-SCT had a poor outcome, with a median overall survival (OS) of around 1-2 years. Significant progress has been achieved in the last decade with the use of brentuximab vedotin (BV) or check-point inhibitors (CPI) and the increasing use of haploidentical transplant. However, little information is available about the characteristics and real-world outcomes of patients with HL relapsing after auto-SCT in the current era. To assess prognosis of patients with recurrent-HL post auto-SCT over time, we analyzed the European Blood and Marrow Transplant registry data of 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. A specific questionnaire was sent to all participant centers to obtain additional data regarding characteristics of the patients, treatment of relapse and outcome after auto-SCT failure. Detailed data were collected for 760 patients [median age 32; interquartile range (IQR) 25-42] included in this study. After a median follow-up for alive patients of 57 months (IQR: 29-89), the 4-year OS after relapse for the 760 included patients was 46% (95%CI: 43-50) and similar to that of 1021 non-included patients (45%, 95%CI: 41-48). The 4-year OS after relapse continuously increased from 35% (95%CI: 27-45) for 136 patients relapsing in 2006-2008, to 43% (95%CI: 37-49) for 258 patients relapsing in 2009-2011, 49% (95%CI: 43-56) for 238 patients relapsing in 2012-2014, and 61% (95%CI: 52-72) for 128 patients relapsing in 2015-2017 (p=0.001) (Figure 1). Improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p=0.01) but not in those with a late relapse (p=0.6). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status at relapse, bulky disease at relapse, extranodal disease at relapse and presence of B-symptoms at relapse were associated with a worse OS. Regarding treatment at relapse, BV was used in 233 patients (31%) after a median of 2 months from relapse (IQR: 0.8-8), predominantly as first treatment of relapse (155 patients). BV use increased over the 4 time periods from 3% to 19%, 49% and 49% respectively, and resulted in a complete remission (CR) in 46% and a partial response (PR) in 32%. The 4-year OS from BV use for relapse after auto-SCT was 56% (95%CI: 49-64). CPI were used in 91 patients (12%) including nivolumab in 75 patients and pembrolizumab in 12 patients after a median of 18 months from relapse (IQR: 5-35). CPI use increased over the 4 time periods from 1% to 4%, 14% and 35% respectively, and resulted in a CR of 44%, PR 32%, with a 4-year OS from CPI use of 44% (95%CI: 30-63). Finally, a second SCT (SCT2) was performed in 330 patients (43%) predominantly allogeneic SCT (285 patients, 86%) including a haploidentical SCT in 54 patients (16%). SCT2 was performed in 40% and 37% of patients relapsing in 2006-2008 and 2009-2011 respectively but its use increased to 49% and 51% of patients relapsing in 2012-2014 and 2015-2017 respectively. Four-year OS after SCT2 was 55%. In conclusion, outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse, possibly reflecting, among other factors, the efficacy of post-transplant salvage including BV, CPI and second transplant. These large-scale real-world data can serve as benchmark for future studies in that setting.