Dataset Information

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.

SUBMITTER: Jeong AR

PROVIDER: S-EPMC11363031 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Jeong Ah-Reum AR Trando Aaron H AH Thomas Sean D SD Riviere Paul P Sakowski Patrick J PJ Sokol Ethan S ES Goodman Aaron M AM Kurzrock Razelle R

Therapeutic advances in medical oncology 20240828

<h4>Background</h4>The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.<h4>Objectives</h4>This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.<h4>Design</h4>This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University ...[more]

PMID: 39220298

Similar Datasets

Project description:BACKGROUND:Abnormalities in the KEPA1-NRF2 pathway have a role in cancer progression, metastasis, and resistance to chemo- and radiotherapies. Persistent activation of NRF2 associates with poor prognosis across different cancer types. However, the beneficial therapeutic strategy to harness this pathway in cancer remains unclear. This study aimed to investigate the clinical outcome with immunotherapy in NFE2L2/KEAP1 mutant population. MATERIALS AND METHODS:We investigated the correlation between NFE2L2/KEAP1 mutations and tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) expression status to identify the therapeutic vulnerability. For this purpose, relevance analysis with TMB value was performed in 9,040 patients with cancer, and relevance analysis with PD-L1 expression was performed in 3,457 patients. The Memorial Sloan Kettering Cancer Center (MSKCC) database and real-world evidence were used to assess the immunotherapy response in NFE2L2/KEAP1 mutant subsets. RESULTS:NFE2L2/KEAP1 mutations occurred in various cancers, and the highest mutation incidences occurred in lung squamous cell carcinoma (LUSC) at 19.16% (NFE2L2) and 10.31% (KEAP1). We confirmed that higher TMB value and PD-L1 expression were associated with NFE2L2/KEAP1 mutations compared with wild-type, especially in non-small lung cancer. MSKCC database analysis showed the improved survival of patients with NFE2L2/KEAP1 mutant with immunotherapy compared with other treatments (median overall survival 22.52 VS 12.89, p = .0034). Real-world evidence further confirmed the efficacy of immunotherapy in the mutant population. CONCLUSION:Our study revealed that patients with NFE2L2/KEAP1 mutant could achieve improved outcomes from immunotherapy than the other treatments. These findings may broaden the application of immune checkpoint blockade to patients harboring NFE2L2/KEAP1 mutations. IMPLICATIONS FOR PRACTICE:NFE2L2/KEAP1 alterations occur frequently in multiple cancer types and are associated with poor prognosis; however, the efficacious strategy to inhibit this pathway in cancer is poorly understood. This study was designed to analyze the mutational characteristics of NFE2L2/KEAP1 alterations in 9,243 Chinese patients. The highest mutation incidences occurred in lung squamous cell carcinoma at 19.16% (NFE2L2) and 10.31% (KEAP1). Relevance analysis showed the NFE2L2/KEAP1 mutant subsets were associated with higher tumor mutational burden value and programmed death-ligand 1 expression. Clinical data further confirmed NFE2L2/KEAP1 mutations correlate with improved outcome with immunotherapy. These findings suggest the clinical application of immunotherapy in the NFE2L2/KEAP1 mutant population.

Dataset Information

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

Background

Objectives

Design

Methods

Results

Conclusion

Trial registration

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets