A SHORT (x3) NIVOLUMAB BEFORE BGD CHEMOTHERAPY IMPROVES THE REMISSION RATE IN RELAPSED/REFRACTORY HODGKIN LYMPHOMA: N-BURGUND TRIAL OF THE POLISH LYMPHOMA RESEARCH GROUP

Abstract

Introduction: Achieving complete metabolic remission (CMR) before autologous hematopoietic cell transplantation aHCT in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma patients (pts) improves their long-term outcomes. BGD (bendamustine, gemcitabine, dexamethasone) in a second line induces CMR in about 70% of r/r HL pts (Paszkiewicz-Kozik et al., Hematological Oncology, 42, Suppl, p364 2023). The phase 2 N-BURGUND trial (EudraCT 2021-002630-17) evaluates the efficacy and safety of a very short course of Nivolumab (N) (3 cycles) followed by 2 (up to maximum 4) cycles of BGD in r/r HL pts before aHCT having hypothesized that addition of Nx3 will improve the response to BGD (CMR) by 15%. Here, we present the efficacy and safety results of the enrolled patients.

Methods: Patients aged ≥ 18 years with r/r advanced stage (IIB-IV) HL after first-line treatment were eligible and received N 240 mg IV Q2W for three cycles followed by PET_NIV and 2 to max four cycles of BGD (bendamustine 90 mg/m² D1,2; gemcitabine 800 mg/m² on D1,4; dexamethasone 40 mg on D1–4) combined with CD34+ cell mobilization followed by PET_2BGD. 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 PET_BGD-negativity response in patients after two cycles of BGD. The secondary endpoints are PET_NIVO response and the results of circulating tumor DNA assessment at the time of PET examinations.

Results: Between December 2022 and November 2024, 86 pts (50% females) with r/r cHL were enrolled from 9 centers affiliated with the PLRG. Median (range) age was 36 years (20–71); 71 (83%) patients received ABVD, 2 (2%) BV+AVD, and 13 (15%) BEACOPPesc in the first line. Forty pts (47%) were primary refractory, including 6 to BEACOPPesc and 2 to BV+AVD; twenty-five (29%) pts had an early relapse (< 12 months), whereas the remaining 21 (24%) had a late relapse. All patients have completed 3 × N and 2 × BGD. Eighty-four PET_NIVO, and 78 PET_BGD results were available at the time of submission. The PET_NIVO negativity rate was 34%. Afterward, the PET_BGD negativity rate increased to 86%. In 76 pts with two PET assessments available, BGD improved response in 37 (48%) 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 during the study.

Conclusion: A very short Nivolumab induction followed by a standard second-line BGD chemotherapy is well tolerated in pts with r/r HL, improving the response to BGD (CMR rate) from a historical 70% to 86%.

Research funding declaration: Medical Research Agency, Poland

Keywords: chemotherapy; immunotherapy

Potential sources of conflict of interest:

J. M. Zaucha

Stock ownership: Takeda, BMS, Roche, Abbvie, janssen, Sobi

Honoraria: Roche

E. Paszkiewicz-Kozik

Consultant or advisory role: ABBVIE, TAKEDA, ROche,

Honoraria: abbvie, takeda, roche

Educational grants: Roche, Takeda

M. Taszner

Honoraria: Sobie

Educational grants: Takeda

J. Rybka

Honoraria: Takeda

Educational grants: BMS, ABBVIE

C. Voltin

Consultant or advisory role: Novartis Radiopharmaceuticals GmbH, Novartis Pharma GmbH.

M. Kurlapski

Educational grants: Takeda

T. Wróbel

Stock ownership: Takeda, Roche, Abbvie, BMS

Honoraria: Amgen, Janssen