Higher tumor mutational burden and PD-L1 expression correlate with shorter survival in hematologic malignancies.

IF 4.3 2区医学 Q2 ONCOLOGY Therapeutic Advances in Medical Oncology Pub Date : 2024-08-28 eCollection Date: 2024-01-01 DOI:10.1177/17588359241273053

Ah-Reum Jeong, Aaron H Trando, Sean D Thomas, Paul Riviere, Patrick J Sakowski, Ethan S Sokol, Aaron M Goodman, Razelle Kurzrock

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Abstract

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 R ² = 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.

Trial registration: ClinicalTrials.gov NCT02478931.

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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。

背景：在血液系统恶性肿瘤中，肿瘤突变负荷（TMB）和程序性死亡配体1（PD-L1）表达对预后的影响研究甚少：对血液系统恶性肿瘤中肿瘤突变负荷（TMB）和程序性死亡配体1（PD-L1）表达的预后影响研究较少：本研究旨在更好地了解TMB和PD-1/PD-L1在血液恶性肿瘤中的特征和预后价值：这项真实世界研究的对象是在加州大学圣地亚哥分校摩尔斯癌症中心进行了新一代测序（NGS）（基础医学）的血液恶性肿瘤患者（2014-2018年）：通过 NGS 测定 TMB。PD-L1表达（肿瘤比例评分，TPS）通过免疫组化进行测量（分为高表达（⩾50%）、低表达（1-49%）和阴性表达）：在388名可评估的患者中，最常见的诊断是B细胞非霍奇金淋巴瘤（NHL）（35%）和费城染色体阴性骨髓增生性疾病（16%）。TMB中位数为1.6个突变/Mb（范围0-46.83）。48名患者（12%）的TMB⩾10突变/Mb，其中90%为B细胞或T细胞NHL。在85份可获得PD-L1评分的样本中，11份为高分；26份为低分；48份无肿瘤细胞表达。PD-L1 TPS阳性（⩾1%）最常见于T细胞NHL（7/9（77%）例），其次是B细胞NHL（21/51（41%）例）。TMB⩾4突变/Mb和PD-L1评分⩾1%与诊断后较短的总生存期（OS）显著相关，危险比（HR）=1.46（P = 0.02，95% 置信区间 (CI) 1.05-2.03) 和 HR = 2.11 (p = 0.04，95% CI 1.04-4.30)；当 PD-L1 ⩾50% 与 p = 0.02，95% CI 1.19-6.59 相比，这种关系更为明显。）TMB越高，PD-L1阳性率越高，两者之间的相关性显著但较弱（皮尔逊相关系数R 2 = 0.04，P = 0.04）：结论：TMB ⩾4突变/Mb和PD-L1 TPS阳性是不良预后因素，与血液恶性肿瘤较短的OS相关：试验注册：ClinicalTrials.gov NCT02478931。

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来源期刊

Therapeutic Advances in Medical Oncology ONCOLOGY-

CiteScore

8.20

自引率

2.00%

发文量

160

审稿时长

15 weeks

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).