THE ROLE OF STEM CELL TRANSPLANTATION AS CONSOLIDATION THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA TREATED WITH CHECKPOINT INHIBITORS: ITALIAN MULTICENTER EXPERIENCE

Background Background There is no agreement on the role and positioning of stem cell transplantation (SCT) in patients (pts) with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) who undertake treatment with checkpoint inhibitors (CPI). Aims Aims The aim of this study is to evaluate the real-world outcomes of R/R cHL pts treated with CPI, particularly the use of consolidation with autologous (autoSCT) and allogeneic SCT (alloSCT). Methods Methods Observational, retrospective, multicenter study which enrolled consecutive pts with R/R cHL aged 18-70 years, treated with at least one dose of CPI (nivolumab or pembrolizumab) monotherapy in Italy from January 2016 to June 2023. Primary objective was the proportion of pts who received consolidation with alloSCT. Responses and survival outcomes were defined according to Lugano criteria (Cheson BD et al. 2014 and 2016). Survival curves were estimated with Kaplan-Meier method. Results Results We enrolled 126 pts from 15 Italian centers. Median age at CPI start was 36 years (18-70), 54% were males, 95% received ABVD as first-line therapy, 64% were primary refractory, 51% previously received autoSCT and 98% brentuximab vedotin. Eighty-six pts (68%) were treated with pembrolizumab, 40 (32%) with nivolumab. Overall response rate to CPI treatment was 81%, with 49% complete responses (CRs). One-hundred and seven pts (85%) were considered fit for alloSCT, and among those 62 (58%) were planned to receive alloSCT. Ultimately, 41 pts (32%) received an alloSCT, 36 (29%) consolidated with autoSCT and 49 (39%) received no consolidation. Reasons for not performing alloSCT in candidates were progressive disease (PD) (n=9), donor unavailability (n=4), patient’s refusal or comorbidities (n=4), others (n=4). Twenty-nine out of 41 allo-transplanted pts (70%) had already received an autoSCT before CPI. Reasons for not administering a consolidation after CPI were age/comorbidity (n=19), center’s choice (n=9), alloSCT refusal or donor unavailability (n=9), PD (n=7), other (n=5). In pts who consolidated with alloSCT or autoSCT, median PFS and OS were not reached at a median follow-up of 27 (range 7-90) and 47.5 months (range 4-99) from CPI treatment, respectively. 48-months PFS probability were 80.6% and 81% for alloSCT and autoSCT recipients, respectively. Transplant-related mortality after alloSCT was 14.6%. In non-consolidated pts, at a median follow-up of 21 months, median PFS was 27 months (95% confidence interval: 16-not reached). Seventeen pts (35%) were still receiving CPI treatment at last follow-up; the main reason for interruption was PD, in 18/32 pts (56%). In pts who received SCT consolidation there was no difference in terms of PFS according to the obtainment of a CR with CPI (p=0.93 for alloSCT and p=0.6 for autoSCT). Instead, pts who did not consolidate had a significantly poorer outcome if they did not obtain a CR with CPI treatment (median PFS not reached vs 11 months; p<0.001) - Figure 1. Summary/Conclusion Summary/Conclusion Outcomes after autoSCT and alloSCT consolidation are excellent, regardless of the response achieved with CPI treatment; as expected, alloSCT was burdened by higher toxicity. Pts who achieved a CR with CPI showed good outcomes even without consolidation, however autoSCT should be considered, if not performed before. Pts who do not achieve/loss the CR and have already performed autoSCT can be considered for alloSCT. Those who do not achieve a CR and do not consolidate have the worst outcome.