Abstract T108

Primary Analysis of the GHSG Pembro-CORE Trial: PET-Adapted PD-1-Based Salvage Therapy Omitting High-Dose Chemotherapy in First-Relapsed Hodgkin Lymphoma

Background: Standard therapy for relapsed/refractory classical Hodgkin lymphoma (r/r cHL) consists of salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem-cell transplantation (ASCT). Although effective, this approach is associated with substantial acute and long-term toxicity, and a major unmet need for HDCT-free strategies remains. Anti-PD1-based salvage combinations have shown high complete metabolic response rates (CMR) and may allow selected patients to avoid HDCT/ASCT.

Methods: Pembro-CORE is a prospective, open-label, multicenter phase II trial conducted at four German sites. Transplant-eligible patients aged 18–65 years with first relapsed or primary refractory cHL received 1x pembrolizumab followed by chemoimmunotherapy adapted by interim PET after 1x pembrolizumab and 2x P-ICE. PET-negative patients received 2 additional P-ICE, whereas PET-positive patients switched to 4x P-DHAP. Patients achieving PET negativity received 8x pembrolizumab maintenance. Stem-cell apheresis was mandatory; patients with persistent PET positivity were recommended to undergo off-trial HDCT/ASCT. The primary endpoint was centrally reviewed CMR after completion of 4x chemoimmunotherapy.

Results: 29 patients were enrolled (median age 38 years; 59% male; 52% advanced-stage at initial diagnosis; 93% BEACOPP-like-pretreated; 14% primary refractory). At the primary endpoint restaging CMR was achieved in 26/29 patients (90%). After 2 cycles of chemoimmunotherapy, the CMR rate was 57%. Only 5/29 patients (17%) subsequently underwent HDCT/ASCT. With a median follow-up of 13.2 months, 9 patients (31%) experienced progression/relapse, including 7 patients who had achieved CMR at the primary endpoint assessment. No deaths occurred. All patients experienced at least one adverse event. Serious adverse events occurred in 10/29 (34%), mainly infections (n=5), while one patient developed autoimmune colitis (all events resolved).

Conclusions: PET-adapted pembrolizumab-chemotherapy induces a high CMR rate of 90% in first r/r cHL. However, the substantial relapse rate despite short follow-up, including relapses among patients who achieved PET-negativity at the primary endpoint restaging indicates that Deauville score-based stratification alone appears insufficient to identify patients who can safely omit HDCT. Further studies exploring HDCT-free strategies, tailored by biologically defined patient subgroups and dynamic response assessment, are warranted.