Abstract P107

A short course of nivolumab (N) followed by chemotherapy BGD and autologous transplantation (aHCT) as the salvage treatment for relapsed/refractory (r/r) Hodgkin Lymphoma (cHL) patients – the preliminary results of the N-BURGUND trial of PLRG

Introduction: Achieving complete metabolic remission (CMR) before aHCT in patients with r/r HL improves their long-term outcomes. BGD induces CMR in about 50-65% of r/r HL pts (Swoboda T et al, Ann Hematol 2021). The phase 2 N-BURGUND trial (EudraCT 2021-002630-17) evaluates the efficacy and safety of a short course of Nivolumab (N) (3 cycles) followed by 2 (max. 4) cycles of BGD in r/r HL pts before aHCT having hypothesized that addition of N will improve the response to BGD. We present the preliminary analysis of efficacy and safety in enrolled pts.

Methods: Patients aged ≥18 years with r/r advanced stage (IIB-IV) HL after first-line treatment received N 240 mg IV Q2W for 3 cycles followed by PETNIV and 2-4 cycles of BGD (bendamustine 90mg/m2 D1,2; gemcitabine 800 mg/m2 on D1,4; dexamethasone 40 mg on D1–4.) combined with CD34+ cell mobilization followed by PET2BGD. Patients achieving CMR (Deauville score 1-3 assessed by the Central Reviewer Panel) are subjected to aHCT. The primary endpoint for this analysis is centrally assessed PETBGD-negativity response in patients who completed at least 2 cycles of BGD. The secondary end-point is PETNIVO response and the results of tumor-free DNA assessment at the time of PET examinations.

Results: At a date cut-off (May 20, 2024), 59 pts with r/r cHL were enrolled from 9 centers affiliated with the PLRG. Median (range) age was 32,5 years (19-65); 83% of patients received ABVD, and 17% BEACOPPesc in the first line. 54% of pts were primary refractory; 34% pts had an early relapse (<12 months) whereas the remaining (12%) had a late relapse. So far, 37 pts have completed 3 x N and 2 x BGD. The PETBGD negativity rate was 86%, whereas the PETNIVO negativity rate was 40,5%. BGD improved response in 17(46%) pts. One patient required two more BGD cycles to achieve CMR. Grade ≥3 adverse events (AEs) (26.5% of all AEs) occurred in 13 pts (22% of all pts). Drug-related grade 4 AEs included: flare syndrome and anemia caused by pure red cell aplasia, which resolved after 6 months of treatment with steroids, rituximab, and bortezomib. Immune-mediated AEs (3,6% of all AEs) occurred in 5% of patients who received nivolumab. The most common AE was rash (14.5%) (Figure 1). There were no deaths.

Conclusion: A short Nivolumab induction followed by standard second-line BGD chemotherapy is well tolerated in pts with r/r HL, improving the response to BGD to 86% PET negativity. There were no new safety issues, and the study is ongoing.