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

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.