ISHL13 Abstract T104

Brentuximab Vedotin - ESHAP Significantly Increases the Metabolic Complete Remission Rate versus ESHAP in Relapsed Classical Hodgkin’s Lymphoma. Final Results of the BRESELIBET Prospective Trial.

Background: Best salvage treatment for relapsed/refractory HL (RRHL) is unknown; superiority of brentuximab vedotin (BV) + chemotherapy (CT) vs CT alone has never been tested in randomized trials. It is also unknown if consolidation with BV could eventually spare auto-HCT in good risk RRHL patients.

Objectives: BRESELIBET (ClinicalTrials.gov ID: NCT04378647) is a phase 2b prospective clinical trial that evaluates the efficacy of BRESHAP vs ESHAP in RRHL, followed by BV consolidation (13 or 16 cycles, respectively, 1.8 mg/kg iv q3wks) in patients attaining a mCR. Primary efficacy endpoint was mCR (DS 1-3) after 3 cycles.

Results: 160 adult pts with RRHL were included from 05/2020 to 10/2023 and 151 [88 (58.3%) males, median age of 39 years (18-65)] were randomized 1:1 between BRESHAP (n=76) and ESHAP (n=75). BRESHAP and ESHAP arms were well balanced; 53 pts (35.5%) were primary refractory, 79 pts (52.3%) had nodular sclerosis subtype, 79 (52.3%) relapsed in advanced stage (III-IV), 24 (15.9%) had > 1 extranodal site, 13 (8.6%) bulky mass and 37 (24.5%), B symptoms. The primary endpoint was met: mCR was 69.7% in BRESHAP pts vs 48.0% in EHAP (p=0.007). Final logistic regression model indicated that not only treatment arm (BRESHAP vs ESHSP, p=0.003) but also disease status (primary refractory vs early relapse vs late relapse, p=0.007) and extranodal disease (no vs 1 site vs > 1 site, p<0.001) were independent prognostic factors for mCR. 52 treatment-related adverse events (TRAE) grade 3-4 have been reported in the BRESHAP arm vs 63 grade 3-4 TRAE in ESHAP. No cases of grade 3-4 peripheral sensory or motor neuropathy were reported. 73 pts entered into the consolidation phase and received 13 (1-16) cycles of BV; there have been 11 relapses (15%) after 5 (2 – 16) cycles of BV, 9 of them during the first year. No relapses have happened during the follow up and 38 patients have finished BV therapy. Ten patients discontinued consolidation due to AE (9 polyneuropathy, 1 pneumonitis) and 11 due to disease relapse. With a median follow up of 10 (1 – 36.5) mo after the beginning of consolidation, PFS is 79.4% (95%CI 67.9 – 90.9) at 24 mo. Conclusions: BRESELIBET trial demonstrates that the association of BV to ESHAP results in a significantly higher proportion of mCR than ESHAP alone with no additional toxicity signals; BV consolidation might eventually substitute auto-HCT in patients that achieve a mCR after salvage therapy.