Jeong Ah-Reum, Trando Aaron H, Thomas Sean D, Riviere Paul, Sakowski Patrick J, Sokol Ethan S, Goodman Aaron M, Kurzrock Razelle
Division of Blood and Marrow Transplantation, Department of Medicine, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0658, USA.
Division of Blood and Marrow Transplantation, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Ther Adv Med Oncol. 2024 Aug 28;16:17588359241273053. doi: 10.1177/17588359241273053. eCollection 2024.
The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.
This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.
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).
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.
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 ( = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 ( = 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, = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient = 0.04, = 0.04).
TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies.
ClinicalTrials.gov NCT02478931.
肿瘤突变负荷（TMB）和程序性死亡配体1（PD-L1）表达对血液系统恶性肿瘤预后的影响研究较少。
本研究旨在更好地了解TMB和PD-1/PD-L1在血液系统恶性肿瘤中的特征及预后价值。
这项真实世界研究在加利福尼亚大学圣地亚哥分校穆尔斯癌症中心（2014 - 2018年）接受下一代测序（NGS，Foundation Medicine）的血液系统恶性肿瘤患者中进行。
通过NGS检测TMB。通过免疫组织化学检测PD-L1表达（肿瘤比例评分，TPS）（分为高（⩾50%）、低（1 - 49%）和阴性（<1%））。数据来自电子病历。
在388例可评估患者中，最常见的诊断为B细胞非霍奇金淋巴瘤（NHL）（35%）和费城染色体阴性骨髓增殖性疾病（16%）。中位TMB为1.6个突变/Mb（范围，0 - 46.83）。48例患者（12%）的TMB⩾10个突变/Mb，其中90%为B细胞或T细胞NHL。在85份有可用PD-L1评分的样本中，11份为高表达；26份为低表达；48份无肿瘤细胞表达。PD-L1 TPS阳性（⩾1%）在T细胞NHL中最常见（7/9（77%）例），其次是B细胞NHL（21/51（41%）例）。TMB⩾4个突变/Mb和PD-L1评分⩾1%与诊断后的总生存期（OS）缩短显著相关，危险比（HR）分别为1.46（=0.02，95%置信区间（CI）1.05 - 2.03）和HR = 2.11（=0.04，95%CI 1.04 - 4.30）；当使用PD-L1⩾50%与<50%进行比较时，这种关系更明显（HR = 2.80，=0.02，95%CI 1.19 - 6.59）。较高的TMB与较高的PD-L1阳性相关性显著但较弱（Pearson相关系数=0.04，=0.04）。
TMB⩾4个突变/Mb和PD-L1 TPS阳性是不良预后因素，与血液系统恶性肿瘤较短的OS相关。
ClinicalTrials.gov NCT02478931。
