Abstract P118

Autologous hematopoietic cell transplantation remains relevant despite PD-1 inhibitor-based second-line therapy in classic Hodgkin lymphoma: interim results from the Prolgo-HL study

Backgrounds: Recent advances in 2d-line treatment, particularly the incorporation of PD‐1 inhibitors (iPD-1) into salvage regimens before auto-HCT, have markedly improved outcomes in classic Hodgkin lymphoma (cHL). These changes have prompted a re-evaluation of high-dose chemotherapy and auto-HCT, with growing interest in alternative consolidation strategies. This study aimed to assess the feasibility of omitting auto-HCT in patients who achieved an early complete response (CR) to prolgolimab (prolgo).

Methods: This prospective, multicenter, single-arm phase II trial included adult cHL pts after first-line therapy without prior iPD-1 (NCT05757466). The study protocol is shown in Fig. 1. Response was assessed every 3 months by PET-CT (LyRIC). Primary endpoint was ORR, secondary - OS, PFS, DoCR. Intention-to-treat (ITT) population was used for safety, per-protocol (PP) for efficacy. Four pts were excluded from PP due to protocol deviation (n=2), consent withdrawal (n=1), gr 3 AE (n=1).

Results: 32 pts with r/r cHL were enrolled (04.2023-05.2026); 28 were included in the PP analysis. The median follow-up was 24 mo (8-37). After 6 cycles of mono-prolgo, CR was achieved in 9 pts (32%). Among patients with CR, 8 pts (89%) had completed 24 cycles of therapy. In this cohort, relapse occurred in 5 pts (63%). The median PFS was 24 mo (95%CI 24-NA); 2-y PFS was 71% (95%CI 45-100). Eighteen of 19 pts without CR were switched to the prolgo-bendamustine (benda) arm, where ORR was 89% (CR 83%). Among patients who achieved a response, auto-HCT was performed in 7 pts (39%) after prolog+benda, while 1 pt was preparing for auto-HCT. Ten patients did not undergo auto-HCT after completion of the protocol due to patient preference (n=7) or progression (n=1). In patients proceeding directly to auto-HCT, the only event was early post-transplant death; no relapses occurred. Median OS and PFS were not reached; 2-year OS and PFS were 83% (95% CI, 58–100%). Overall, 26 pts completed therapy per protocol. ORR at the end of treatment was 92% (n=24, CR 88%); 2y PFS was 60% (95%CI 43-85); 2y OS was 88% (95%CI 75-100%).

Conclusion: Despite the high CR rates observed with mono-prolgo and prolgo-benda, a high relapse rate was noted, likely associated with omission of auto-HCT in both cohorts, underscoring the importance of this treatment component. Further risk stratification is required to identify a genuinely low-risk subgroup in whom omission of auto-HCT may be a safe and reasonable option.