J. Kuruvilla, P. Armand, A. F. Herrera, V. Ribrag, C. Thieblemont, B. von Tresckow, S. Thompson, K. E. Ryland, R. Z. Yusuf, P. L. Zinzani
{"title":"FINAL SAFETY ANALYSIS IN PARTICIPANTS WITH HEMATOLOGIC MALIGNANCIES WHO RECEIVED ALLOGENEIC STEM CELL TRANSPLANT AFTER PEMBROLIZUMAB THERAPY","authors":"J. Kuruvilla, P. Armand, A. F. Herrera, V. Ribrag, C. Thieblemont, B. von Tresckow, S. Thompson, K. E. Ryland, R. Z. Yusuf, P. L. Zinzani","doi":"10.1002/hon.70094_351","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> Allogeneic stem cell transplant (allo-SCT) carries a relevant risk of transplantation-related mortality (TRM), especially from graft-versus-host disease (GVHD), particularly in patients previously treated with checkpoint inhibitors. Final safety results in participants (pts) with hematologic malignancies who received allo-SCT after pembrolizumab (pembro) therapy across a variety of pembro clinical studies are presented.</p><p><b>Methods:</b> Data were pooled from 10 phase 1–3 studies (KEYNOTE-A33 [NCT04317066], KEYNOTE-013 [NCT01953692], KEYNOTE-155 [NCT02684617], KEYNOTE-051 [NCT02332668], KEYNOTE-B68 [NCT04875195], KEYNOTE-087 [NCT02453594], KEYNOTE-170 [NCT02576990], KEYNOTE-183 [NCT02576977], KEYNOTE-204 [NCT02684292], and MK4280-003 [NCT03598608]). Outcomes of interest included acute and chronic GVHD, incidence of allo-SCT–related adverse events, overall survival (OS), and TRM.</p><p><b>Results:</b> A total of 112 pts were reported to have received allo-SCT, 14 were not included in the analysis (13 received allo-SCT > 2 years after last dose of pembro and 1 had a missing date of allo-SCT). Median duration on study treatment was 5.6 months (range, 0.03–29.7), and median time from last dose of pembro to first allo-SCT was 4.9 months (range, 1–20). Of 98 evaluable pts, 67 pts (68%) received intervening therapy between pembro and allo-SCT. At time of transplant, 47 pts (48%) had active disease, 39 pts (40%) were in remission, and 12 (12%) had unknown disease status. A total of 91 pts (93%) received allo-SCT only; 7 (7%) received autologous SCT followed by allo-SCT. Among 63 pts (64%) who developed GVHD, 52 (53%) experienced acute events (Glucksberg II-IV [<i>n</i> = 34] and Glucksberg III-IV [<i>n</i> = 19]) and 24 (25%) experienced chronic events (mild [<i>n</i> = 11], moderate [<i>n</i> = 8], and severe [<i>n</i> = 5]). The most common sites for chronic GVHD were skin (<i>n</i> = 15), oral mucosa (<i>n</i> = 12), and liver (<i>n</i> = 9). Other predetermined non-GVHD events of clinical interest occurred in 42 pts (43%), categorized as critical illness (30%), febrile syndrome treated with corticosteroids (1%), immune-mediated adverse events (10%), pulmonary complications (14%), and venoocclusive liver disease (3%). The most common predetermined events of clinical interest (≥ 5%) were febrile neutropenia and pneumonia (6% each). The most common of the other adverse events not included in the 5 categories above (≥ 2%) were grade ≤ 2 pyrexia (5%) and rash (2%). Median OS was not reached (NR; 95% CI: NR-NR) post–allo-SCT, with 100-day, 24-month, and 48-month OS rates of 94%, 70%, and 68%, respectively. Estimated TRM rates at 100 days, 24 months, and 48 months were 5%, 21%, and 21%, respectively.</p><p><b>Conclusion:</b> The inclusion of additional pts in this analysis revealed comparable rates of acute and chronic GVHD, OS, and TRM compared to previous studies and historical benchmarks, thus, reinforcing the role of allo-SCT as a viable salvage option post-anti–PD-1 therapy.</p><p><b>Research</b> <b>funding declaration:</b> Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> immunotherapy; stem cell transplant</p><p><b>Potential sources of conflict of interest:</b></p><p><b>J. Kuruvilla</b></p><p><b>Consultant or advisory role:</b> Abbvie, BMS, Gilead/Kite, Merck, Roche, Seattle Genetics</p><p><b>Honoraria:</b> Abbvie, Amgen, AstraZeneca, BMS, Genmab Gilead, GSK, Incyte, Janssen, Karyopharm, Lilly, Merck, Novartis, Pfizer, Roche, Seattle Genetics</p><p><b>Other remuneration:</b> Research Grant/Funding: AstraZeneca, Merck, Novartis, Roche; Other: Karyopharm (DSMB)</p><p><b>P. Armand</b></p><p><b>Consultant or advisory role:</b> Merck, BMS/Celgene, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, AstraZeneca, Genentech/Roche, Xencor, Foresight, ATB Therapeutics, Stelexis</p><p><b>Honoraria:</b> Merck, BMS</p><p><b>Other remuneration:</b> Research Grant/Funding: Kite, Merck, BMS-Celgene, Affimed, Adaptive, Tensha, Otsuka, Sigma Tau, Genentech/Roche, IGM, AstraZeneca</p><p><b>A. F. Herrera</b></p><p><b>Consultant or advisory role:</b> Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Abbvie, Allogene Therapeutics</p><p><b>Other remuneration:</b> Research Funding: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca</p><p><b>V. Ribrag</b></p><p><b>Employment or leadership position:</b> Pegascy</p><p><b>Educational</b> <b>grants:</b> AstraZeneca</p><p><b>Other remuneration:</b> Speaker Bureau: Beigene, Lily, Ipsen; Expert Testimony: AstraZeneca; Research Grant/Funding: GSK, Astex</p><p><b>C. Thieblemont</b></p><p><b>Consultant or advisory role:</b> Roche, Incyte, Novartis, Kyte/Gilead, Amgen, Takeda, BMS</p><p><b>Educational</b> <b>grants:</b> Roche, Incyte, Novartis, Kyte/Gilead, Amgen, Takeda, BMS</p><p><b>Other remuneration:</b> Research Grant/Funding: Roche</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 and Takeda</p><p><b>Honoraria:</b> AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche and Takeda</p><p><b>Educational</b> <b>grants:</b> AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis</p><p><b>Other remuneration:</b> Research Grant/Funding: Esteve (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), and Takeda (Inst)</p><p><b>S. Thompson</b></p><p><b>Employment or leadership position:</b> Merck & Co., Inc.</p><p><b>Stock ownership:</b> Merck & Co., Inc.</p><p><b>K. E. Ryland</b></p><p><b>Employment or leadership position:</b> Merck</p><p><b>Stock ownership:</b> Merck</p><p><b>R. Z. Yusuf</b></p><p><b>Employment or leadership position:</b> Merck</p><p><b>Stock ownership:</b> Merck</p><p><b>P. L. Zinzani</b></p><p><b>Consultant or advisory role:</b> AbbVie, BeiGene, Bristol Myers Squibb, EUSA Pharma, Janssen, Kyowa Kirin, MSD, Novartis, Roche, and Sobi</p><p><b>Honoraria:</b> AbbVie, BeiGene, Bristol Myers Squibb, EUSA Pharma, Janssen, Kyowa Kirin, MSD, Novartis, Roche, and Sobi</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_351","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_351","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: Allogeneic stem cell transplant (allo-SCT) carries a relevant risk of transplantation-related mortality (TRM), especially from graft-versus-host disease (GVHD), particularly in patients previously treated with checkpoint inhibitors. Final safety results in participants (pts) with hematologic malignancies who received allo-SCT after pembrolizumab (pembro) therapy across a variety of pembro clinical studies are presented.
Methods: Data were pooled from 10 phase 1–3 studies (KEYNOTE-A33 [NCT04317066], KEYNOTE-013 [NCT01953692], KEYNOTE-155 [NCT02684617], KEYNOTE-051 [NCT02332668], KEYNOTE-B68 [NCT04875195], KEYNOTE-087 [NCT02453594], KEYNOTE-170 [NCT02576990], KEYNOTE-183 [NCT02576977], KEYNOTE-204 [NCT02684292], and MK4280-003 [NCT03598608]). Outcomes of interest included acute and chronic GVHD, incidence of allo-SCT–related adverse events, overall survival (OS), and TRM.
Results: A total of 112 pts were reported to have received allo-SCT, 14 were not included in the analysis (13 received allo-SCT > 2 years after last dose of pembro and 1 had a missing date of allo-SCT). Median duration on study treatment was 5.6 months (range, 0.03–29.7), and median time from last dose of pembro to first allo-SCT was 4.9 months (range, 1–20). Of 98 evaluable pts, 67 pts (68%) received intervening therapy between pembro and allo-SCT. At time of transplant, 47 pts (48%) had active disease, 39 pts (40%) were in remission, and 12 (12%) had unknown disease status. A total of 91 pts (93%) received allo-SCT only; 7 (7%) received autologous SCT followed by allo-SCT. Among 63 pts (64%) who developed GVHD, 52 (53%) experienced acute events (Glucksberg II-IV [n = 34] and Glucksberg III-IV [n = 19]) and 24 (25%) experienced chronic events (mild [n = 11], moderate [n = 8], and severe [n = 5]). The most common sites for chronic GVHD were skin (n = 15), oral mucosa (n = 12), and liver (n = 9). Other predetermined non-GVHD events of clinical interest occurred in 42 pts (43%), categorized as critical illness (30%), febrile syndrome treated with corticosteroids (1%), immune-mediated adverse events (10%), pulmonary complications (14%), and venoocclusive liver disease (3%). The most common predetermined events of clinical interest (≥ 5%) were febrile neutropenia and pneumonia (6% each). The most common of the other adverse events not included in the 5 categories above (≥ 2%) were grade ≤ 2 pyrexia (5%) and rash (2%). Median OS was not reached (NR; 95% CI: NR-NR) post–allo-SCT, with 100-day, 24-month, and 48-month OS rates of 94%, 70%, and 68%, respectively. Estimated TRM rates at 100 days, 24 months, and 48 months were 5%, 21%, and 21%, respectively.
Conclusion: The inclusion of additional pts in this analysis revealed comparable rates of acute and chronic GVHD, OS, and TRM compared to previous studies and historical benchmarks, thus, reinforcing the role of allo-SCT as a viable salvage option post-anti–PD-1 therapy.
Researchfunding declaration: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
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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