Abstract P116

PD-1 Inhibitor maintenance after Auto-HCT in r/r Classical Hodgkin lymphoma with prior PD-1 exposure: interim phase II results

Background: Maintenance therapy with PD-1 inhibitors after auto-HCT shows promising activity in relapsed/refractory classical Hodgkin lymphoma (r/r cHL). We report interim results of a prospective multicenter study evaluating PD-1 maintenance in patients previously exposed to PD-1 inhibitors.

Methods: This international multicenter phase 2 trial included adult patients with histologically confirmed r/r cHL who underwent auto-HCT after second or later lines of therapy (NCT06812858). Patients received PD-1 inhibitor maintenance per center choice (Fig.1): nivolumab (nivo) 40 mg, 3 mg/kg, or 240 mg IV every 14 days (up to 12 cycles), or pembrolizumab (pembro) 200 mg IV every 21 days (up to 8 cycles). Response evaluation is performed by PET/CT after auto-HCT and following the completion of maintenance therapy (LYRIC).

Results: Forty-seven patients (median age 34 [range 19–56]) were enrolled across four centers (2024–2026). All patients had at least one AETHERA risk factor (median 2, range 1–4). Primary refractory disease occurred in 53% (n=25), early relapse in 28% (n=13). All patients received PD-1 inhibitors prior to auto-HCT, with the last salvage regimen before auto-HCT also including PD-1 inhibitors. Brentuximab vedotin was given before auto-HCT in 32% (n=15). Prior to auto-HCT, the best response to PD-1 inhibitor-based salvage therapy was complete response (CR) in 87% (n=41) and partial response (PR) in 13% (n=6). Pre-HCT status included CR in 83% (n=39), PR in 15% (n=7), and indeterminate response in 2% (n=1). Auto-HCT was performed as consolidation of second-line therapy in 43% (n=20) and third-line or later in 57% (n=27). All patients were in CR prior to the maintenance (PET/CT). Maintenance consisted of full-dose nivo in 36% (n=17), nivo 40 mg in 43% (n=20), and pembro in 21% (n=10). During maintenance, grade 1–2 adverse events (AEs) based on CTCAE v5.0 occurred in 49% (n=23) and grade 3–4 in 4% (n=2), with no treatment-related deaths. The most common AEs were fatigue (13%), thrombocytopenia (13%), upper respiratory tract infection (11%), leukopenia (11%), anemia (9%), and rash (9%). Three patients required therapy discontinuation due to immune-related AEs (grade 3 pneumonitis, grade 4 diarrhea, grade 2 hypothyroidism). After a median follow-up of 10 months (range 1–35), no relapses or deaths were observed.

Conclusion: Interim results demonstrate high efficacy and manageable toxicity in r/r cHL post auto-HCT.