Ah-Reum Jeong, Aaron H Trando, Sean D Thomas, Paul Riviere, Patrick J Sakowski, Ethan S Sokol, Aaron M Goodman, Razelle Kurzrock
{"title":"较高的肿瘤突变负荷和 PD-L1 表达与较短的血液恶性肿瘤生存期相关。","authors":"Ah-Reum Jeong, Aaron H Trando, Sean D Thomas, Paul Riviere, Patrick J Sakowski, Ethan S Sokol, Aaron M Goodman, Razelle Kurzrock","doi":"10.1177/17588359241273053","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.</p><p><strong>Objectives: </strong>This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.</p><p><strong>Design: </strong>This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018).</p><p><strong>Methods: </strong>TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records.</p><p><strong>Results: </strong>In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 (<i>p</i> = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 (<i>p</i> = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, <i>p</i> = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient <i>R</i> <sup>2</sup> = 0.04, <i>p</i> = 0.04).</p><p><strong>Conclusion: </strong>TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT02478931.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241273053"},"PeriodicalIF":4.3000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363031/pdf/","citationCount":"0","resultStr":"{\"title\":\"Higher tumor mutational burden and PD-L1 expression correlate with shorter survival in hematologic malignancies.\",\"authors\":\"Ah-Reum Jeong, Aaron H Trando, Sean D Thomas, Paul Riviere, Patrick J Sakowski, Ethan S Sokol, Aaron M Goodman, Razelle Kurzrock\",\"doi\":\"10.1177/17588359241273053\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.</p><p><strong>Objectives: </strong>This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.</p><p><strong>Design: </strong>This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018).</p><p><strong>Methods: </strong>TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records.</p><p><strong>Results: </strong>In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 (<i>p</i> = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 (<i>p</i> = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, <i>p</i> = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient <i>R</i> <sup>2</sup> = 0.04, <i>p</i> = 0.04).</p><p><strong>Conclusion: </strong>TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT02478931.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"16 \",\"pages\":\"17588359241273053\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363031/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241273053\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241273053","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Higher tumor mutational burden and PD-L1 expression correlate with shorter survival in hematologic malignancies.
Background: The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.
Objectives: This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.
Design: This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018).
Methods: TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records.
Results: In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 (p = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 (p = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, p = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient R2 = 0.04, p = 0.04).
Conclusion: TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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