PD-1-BASED SALVAGE THERAPY FOR RELAPSED AND REFRACTORY HODGKIN LYMPHOMA: A MULTICENTER REAL-WORLD ANALYSIS

Introduction: In relapsed/refractory classical Hodgkin lymphoma (r/r cHL), salvage therapy with chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) yields suboptimal long-term outcomes, with 5-year progression-free survival (PFS) rates below 50%.

PD-1 inhibitor-based salvage regimens have shown superior complete response (CR) rates. For example, P-GVD (pembrolizumab, gemcitabine, vinorelbine, liposomal doxorubicin) achieved CR rates of up to 95% with unprecedented PFS after HD-ASCT (Moskowitz et al., JCO 2021). However, immune checkpoint inhibitors are not EMA-approved for first relapsed in r/r cHL, and European data remain sparse. We evaluated response and outcomes in a European real-world cohort of r/r cHL patients receiving anti-PD-1–based salvage.

Methods: This multicenter, retrospective study included patients from seven European academic centers who received PD-1–based salvage with intent to proceed to HD-ASCT or allogeneic SCT (alloSCT). Response before HD-ASCT/alloSCT was assessed. PFS and overall survival (OS) were estimated using Kaplan-Meier analysis.

Results: We included 43 patients (median age: 31 years, 37.2% female, median prior lines: 2). Salvage regimens were: (I) PD-1 monotherapy (pembrolizumab/nivolumab, n = 7), (II) PD-1 plus chemotherapy [pembrolizumab or nivolumab plus ifosfamide, carboplatin, and etoposide (N-ICE/ P-ICE) or P-GVD, n = 33], or (III) PD-1 (pembrolizumab/nivolumab) + brentuximab vedotin (n = 3).

Overall response rate (ORR) was 92.5%, with 47.5% achieving CR, 45% partial response (PR), and 7.5% stable disease (SD) (40 evaluable patients). BOR/CR rates by salvage regimen were (I): 85.7%/0%; (II): 93.3%/60% (30 evaluable patients); (III): 100%/33.3%. Patients with one prior line receiving PD-1 plus chemotherapy had an ORR of 95% to salvage, with a CR rate of 55%.

Among 40 patients proceeding to HD-ASCT/alloSCT (six alloSCT), best overall response (BOR) and CR rates after transplant were 100% and 96.8% (31 evaluable patients).

With a median follow-up of 15.5 months, 1-year PFS was 91.3% (95% CI: 81.7–100) and OS was 97.6% (95% CI: 93–100). Patients undergoing HD-ASCT/alloSCT (n = 40) had a 1-year PFS of 93.8% (95% CI: 85.4–100) versus 50% (95% CI: 0–100) without transplant. Patients receiving PD-1 plus chemotherapy followed by HD-ASCT in second line had a 1-year PFS of 100% (95% CI: 100–100).

Conclusion: Our findings provide real-world evidence on anti-PD-1–based salvage followed by intensive consolidation in European centers. While previously reported high CR rates after PD-1–based salvage were not reached, outcomes post-HD-ASCT were excellent, supporting the role of PD-1 inhibitors in salvage therapy followed by consolidation HD-ASCT for r/r cHL.

Encore Abstract: EHA 2025

Keywords: Hodgkin lymphoma; immunotherapy

Potential sources of conflict of interest:

U. Schnetzke

Honoraria: Novartis, BMS, Gilead/KITE, Abbvie, Beigene, Janssen, AstraZeneca, SOBI

Educational grants: Novartis, BMS, Gilead/KITE, Abbvie, Beigene, Janssen, AstraZeneca, SOBI

J. C. Hellmuth

Consultant or advisory role: Takeda

Honoraria: Takeda

Educational grants: Beigene

E. Shumilov

Honoraria: Amgen, BMS, Sanofi, Oncopeptides, Gilead, Incyte, Lilly, Takeda

A. Kerkhoff

Honoraria: Abbvie, Amgen, BeiGene, BMS, Novartis, Roche, Recordati, Sobi, Takeda

T. Melchardt

Honoraria: Takeda, MSD

P. J. Bröckelmann

Consultant or advisory role: Hexal, MSD, Need Inc, Stemline and Takeda

Stock ownership: Need Inc

Honoraria: AstraZeneca, BeiGene, BMS/Celgene, Lilly, Merck Sharp & Dohme, Need Inc, Stemline, Takeda

Other remuneration: Received institutional research funding from BeiGene, BMS, Merck Sharp & Dohme and Takeda

B. von Tresckow

Consultant or advisory role: Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Regeneron, Roche, Sobi, Takeda

Honoraria: AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche, Takeda

Educational grants: AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, Novartis

Other remuneration: Research funding from Esteve (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), and Takeda (Inst). Member of steering committees for Regeneron (Inst) and Takeda.