Survival of Hodgkin Lymphoma Patients Treated with Novel Immunotherapies after Autologous Stem Cell Transplantation Failure: A Retrospective Analysis of the Italian Lymphoma Foundation (FIL)

Background: Classical Hodgkin lymphoma (HL) is considered a highly curable disease and nearly 80-90% of patients (pts) may achieve complete remission (CR) with standard chemotherapy (Engert et. al. NEJM 2010).However up to 30% of HL pts experience primary refractory disease or eventually relapse after first-line treatment (Barrington et. al. Blood 2016, Press O et al. Clin Oncol 2016). High-dose chemotherapy followed by autologous hemopoietic stem cell transplantation (autoHSCT) has been showed to be an active salvage treatment in approximately 50% pts with chemosensitive relapse. Before the advent of novel immunotherapies, the median survival duration for pts failing autoHSCT was only 10 months (Vose et. al. Blood 1992). In this setting the introduction of Brentuximab Vedotin (BV) (Younes et. al. JCO 2012) and of the checkpoint inhibitors (CPI) Nivolumab (nivo) (Herrera et. al. Blood 2018) or Pembrolizumab (Chen et.al. Blood 2019) have shown to significant therapeutic active.

Aims: To assess the therapeutic effects of BV and CPI in prolonging PFS and OS in patients with HL r/r post autoHSCT.

Methods: This is an observational, retrospective, multicentric study from 15 centers of the Fondazione Italiana Linfomi (FIL). Adult patients who received salvage treatment with BV or CPI for post autoHSCT r/r HL from January 2015 to June 2018 were included in the analysis; the times of observation was censored in December 2020. Patients that had received pre-autoHSCT BV or CPI, were excluded from the analysis.

Results: 40 pts, 25 treated with BV and 15 with nivo were included into the study. Patients' main characteristics at diagnosis are summarize in Table 1. Overall response was achieved in 23 (56%) pts treated with BV and in 9 (60%) with nivo, respectively. 14 (35%) out of 40 responsive to BV (10 pts) or nivo (4 pts) received allogeneic hemopoietic stem cell transplantation (alloHSCT) consolidation. The median follow-up time from the time of autoHSCT failure of the entire cohort was 36 months (range 2-70). At last follow-up, 32 (80%) pts were in CR, 1 (2%) in PR, while 2 (5%) and 5 (13%) were in SD and PD, respectively. 34 (85%) pts were alive and 6 (15%) have died. In the entire cohort, the median PFS and OS from the time of autoHSCT failure was 36 months and not reached, respectively; the 36-months projected PFS and OS of 50% and 86%, respectively. The median PFS and the 36-months projected OS of pts who received or not received alloHSCT were superimposable (Figure 1).

Conclusion: In this retrospective analysis of pts with HL failing autoHSCT, BV or nivo resulted very active therapeutic salvage therapies. The comparison with historical results of the pre BV/CPI era suggests a major significant improvement both in PFS and OS. A significant proportion of pts received post BV or nivo alloHSCT but the effect of this treatment in prolonging PFS and OS should be further evaluated.