Abstract P125

Three cycles of nivolumab (N) before BGD chemotherapy improves the remission rate before autologous hematopoietic cell transplantation (aHCT) in relapsed/refractory Hodgkin Lymphoma: N-BURGUND trial of the Polish Lymphoma Research Group (PLRG).

Introduction: Achieving complete metabolic response (CMR-Deauville score-DS1-3) before aHCT in patients (pts) with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL) improves the long-term outcomes. BGD chemotherapy (bendamustine 90mg/m2 D1,2; gemcitabine 800 mg/m2 on D1,4; dexamethasone 40 mg on D1–4.) in the 2nd line induces CMR in ca.70% of r/r HL pts. In the phase-2 N-BURGUND trial (EudraCT 2021-002630-17), we test the hypothesis that short exposure to Nivolumab (Nivo) prior to BGD increases CMR rate by 15%.

Methods: Patients aged ≥18 years with r/r stage (IIAX+IIB-IV) HL after 1st-line treatment were eligible and received N 240 mg IV Q2W for 3 cycles followed by PETNIV0 and 2xBGD combined with CD34+ cell mobilization, followed by PETBGD. Responding pts (DS1-4 assessed centrally) are subjected to aHCT and post-transplant brentuximab (BV) if eligible. The primary endpoint is CMR in PETBGD. The secondary endpoints: PETNIV0 response and 2-year progression-free survival (2-Y PFS).

Results: Between 12/22 and 11/24, 86 pts (50% female) with r/r cHL were enrolled across 9 PLRG centers. Median age was 36 years (20-71); 71 (83%) pts received ABVD, 2 (2%) BV+AVD, and 13 (15%) BEACOPPesc as 1st line therapy. 56 (65%) pts were primary refractory, including 12 to BEACOPPesc and 2 to BV+AVD; 50 (58%) pts had an early relapse (<12 months). All pts, except 1, have completed 3xN and 2xBGD. The negative (-) PETNIVO rate was 34,5% (96%CI:23.9%–44.7%), whereas the (-) PETBGD 84% (95%CI 73.9%–90.7%). After 2xBGD all (-) PETNIVO pts had also (-) PETBGD; Out of 55 (+) PETNIVO pts: 41 became (-), the rest remained (+) PETBGD. AHCT was not performed in 10 (12%) pts: 6 because of early progression, 2 because of withdrawal of consent, 1 due to myocardial infarction, and 1 due to lack of compliance. 50 (66%) pts received BV after aHCT at median number 13 (1-16). After median follow-up 24 months 16 pts progressed:1 who withdrew the consent for aHCT, 6 before and 9 after aHCT. 2 pts died: 1 from tuberculosis and 1 from myocardial infarction. 2-Y PFS in ITT population is 76.2% (95%CI:67.3%-86.4%) and per protocol 79% (95%CI:70.2%-88.9%). 2-Y PFS in pts with (-) PETNIVO is 93.1% (95%CI:84.3%-100%) and significantly better compared to (+) PETNIVO 67.4% (95% CI: 55.6%-81.7%) with HR: 0.20 (95% CI:0.05-0.86), p=0.016, Figure.

Conclusion: A short Nivo prior to standard 2nd line BGD improves CMR from historical 70% to 84%. CMR after 3xNivo identifies pts with excellent 93% PFS.