Courtney H Coschi, Keyue Ding, Justin Tong, Dongsheng Tu, Christopher O'Callaghan, Natasha B Leighl, Francisco Vera-Badillo, Rosalyn A Juergens, Desiree Hao, Lesley Seymour, Daniel J Renouf, Eric Chen, Pierre-Olivier Gaudreau, Andrea S Fung
{"title":"大麻素对免疫检查点抑制剂反应的影响：CCTG对个体患者数据的汇总分析。","authors":"Courtney H Coschi, Keyue Ding, Justin Tong, Dongsheng Tu, Christopher O'Callaghan, Natasha B Leighl, Francisco Vera-Badillo, Rosalyn A Juergens, Desiree Hao, Lesley Seymour, Daniel J Renouf, Eric Chen, Pierre-Olivier Gaudreau, Andrea S Fung","doi":"10.1080/1750743X.2025.2485012","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.</p><p><strong>Methods: </strong>Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (<i>n</i> = 684) were pooled. Cochran - Mantel - Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).</p><p><strong>Results: </strong>Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (<i>p</i> = 0.15), PFS (<i>p</i> = 0.12), OS (<i>p</i> = 0.35) or incidence of grade 1/2 or 3/4 irAEs (<i>p</i> = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.</p><p><strong>Conclusion: </strong>Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.</p>","PeriodicalId":13328,"journal":{"name":"Immunotherapy","volume":" ","pages":"257-268"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036482/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data.\",\"authors\":\"Courtney H Coschi, Keyue Ding, Justin Tong, Dongsheng Tu, Christopher O'Callaghan, Natasha B Leighl, Francisco Vera-Badillo, Rosalyn A Juergens, Desiree Hao, Lesley Seymour, Daniel J Renouf, Eric Chen, Pierre-Olivier Gaudreau, Andrea S Fung\",\"doi\":\"10.1080/1750743X.2025.2485012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.</p><p><strong>Methods: </strong>Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (<i>n</i> = 684) were pooled. Cochran - Mantel - Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).</p><p><strong>Results: </strong>Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (<i>p</i> = 0.15), PFS (<i>p</i> = 0.12), OS (<i>p</i> = 0.35) or incidence of grade 1/2 or 3/4 irAEs (<i>p</i> = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.</p><p><strong>Conclusion: </strong>Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.</p>\",\"PeriodicalId\":13328,\"journal\":{\"name\":\"Immunotherapy\",\"volume\":\" \",\"pages\":\"257-268\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036482/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1750743X.2025.2485012\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1750743X.2025.2485012","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data.
Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.
Methods: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran - Mantel - Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).
Results: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.
Conclusion: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.
期刊介绍：
Many aspects of the immune system and mechanisms of immunomodulatory therapies remain to be elucidated in order to exploit fully the emerging opportunities. Those involved in the research and clinical applications of immunotherapy are challenged by the huge and intricate volumes of knowledge arising from this fast-evolving field. The journal Immunotherapy offers the scientific community an interdisciplinary forum, providing them with information on the most recent advances of various aspects of immunotherapies, in a concise format to aid navigation of this complex field.
Immunotherapy delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this vitally important area of research. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.
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