H. Tharmaseelan, L. M. Sgonina, I. Bühnen, U. Schnetzke, J. Meißner, M. Sellmayr, D. Beverungen, J. C. Hellmuth, E. Shumilov, A. Kerkhoff, T. Melchardt, P. J. Bröckelmann, P. Borchmann, B. von Tresckow
{"title":"PD-1-BASED SALVAGE THERAPY FOR RELAPSED AND REFRACTORY HODGKIN LYMPHOMA: A MULTICENTER REAL-WORLD ANALYSIS","authors":"H. Tharmaseelan, L. M. Sgonina, I. Bühnen, U. Schnetzke, J. Meißner, M. Sellmayr, D. Beverungen, J. C. Hellmuth, E. Shumilov, A. Kerkhoff, T. Melchardt, P. J. Bröckelmann, P. Borchmann, B. von Tresckow","doi":"10.1002/hon.70094_358","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> 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%.</p><p>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., <i>JCO</i> 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.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> We included 43 patients (median age: 31 years, 37.2% female, median prior lines: 2). Salvage regimens were: (I) PD-1 monotherapy (pembrolizumab/nivolumab, <i>n</i> = 7), (II) PD-1 plus chemotherapy [pembrolizumab or nivolumab plus ifosfamide, carboplatin, and etoposide (N-ICE/ P-ICE) or P-GVD, <i>n</i> = 33], or (III) PD-1 (pembrolizumab/nivolumab) + brentuximab vedotin (<i>n</i> = 3).</p><p>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%.</p><p>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).</p><p>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 (<i>n</i> = 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).</p><p><b>Conclusion:</b> 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.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> Hodgkin lymphoma; immunotherapy</p><p><b>Potential sources of conflict of interest:</b></p><p><b>U. Schnetzke</b></p><p><b>Honoraria:</b> Novartis, BMS, Gilead/KITE, Abbvie, Beigene, Janssen, AstraZeneca, SOBI</p><p><b>Educational</b> <b>grants:</b> Novartis, BMS, Gilead/KITE, Abbvie, Beigene, Janssen, AstraZeneca, SOBI</p><p><b>J. C. Hellmuth</b></p><p><b>Consultant or advisory role:</b> Takeda</p><p><b>Honoraria:</b> Takeda</p><p><b>Educational</b> <b>grants:</b> Beigene</p><p><b>E. Shumilov</b></p><p><b>Honoraria:</b> Amgen, BMS, Sanofi, Oncopeptides, Gilead, Incyte, Lilly, Takeda</p><p><b>A. Kerkhoff</b></p><p><b>Honoraria:</b> Abbvie, Amgen, BeiGene, BMS, Novartis, Roche, Recordati, Sobi, Takeda</p><p><b>T. Melchardt</b></p><p><b>Honoraria:</b> Takeda, MSD</p><p><b>P. J. Bröckelmann</b></p><p><b>Consultant or advisory role:</b> Hexal, MSD, Need Inc, Stemline and Takeda</p><p><b>Stock ownership:</b> Need Inc</p><p><b>Honoraria:</b> AstraZeneca, BeiGene, BMS/Celgene, Lilly, Merck Sharp & Dohme, Need Inc, Stemline, Takeda</p><p><b>Other remuneration:</b> Received institutional research funding from BeiGene, BMS, Merck Sharp & Dohme and Takeda</p><p><b>B. von Tresckow</b></p><p><b>Consultant or advisory role:</b> 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</p><p><b>Honoraria:</b> AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche, Takeda</p><p><b>Educational</b> <b>grants:</b> AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, Novartis</p><p><b>Other remuneration:</b> Research funding from Esteve (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), and Takeda (Inst). Member of steering committees for Regeneron (Inst) and Takeda.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_358","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_358","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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