Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients

Césaire, Mathieu; Rambeau, Audrey; Clatot, Florian; Johnson, Alisson; Heutte, Natacha; Thariat, Juliette

doi:10.1007/s00405-022-07800-1

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…A previous study of 105 patients with recurrent metastatic esophageal cancer receiving immunotherapy showed that lymphopenia is associated with a poorer immunotherapy prognosis in these patients (41). In another study of patients treated with nivolumab for recurrent/ metastatic head and neck cancer, head and neck cancer, persistence of lymphopenia during immunotherapy was shown to be a predictor of worse OS (42). One attractive question at current stage is whether a prompt recovery from TRL may hold significance in enhancing the prognosis of patients with lung cancer on ICIs.…”

Section: Discussionmentioning

confidence: 96%

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis

Zhang,

Huang,

2023

Front. Oncol.

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BackgroundTreatment-related lymphopenia (TRL) is common in patients with lung cancer, particularly in those with radiotherapy. However, the influence of TRL on the efficacy of immune checkpoint inhibitors (ICIs) for patients with lung cancer remains poorly understood. We performed a systematic review and meta-analysis to investigate the influence of TRL on survival of lung cancer patients on ICIs.MethodsIn order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and the Web of Science to identify observational studies with longitudinal follow-up. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity.ResultsTen cohort studies with 1130 lung cancer patients who were treated with ICIs were included. Among them, 427 (37.8%) had TRL. Pooled results showed that compared to patients without TRL, patients with TRL were associated with poor progression-free survival (hazard ratio [HR]: 2.05, 95% confidence interval [CI]: 1.62 to 2.60, p < 0.001; I2 = 22%) and overall survival (HR: 2.69, 95% CI: 2.10 to 3.43, p < 0.001; I2 = 0%). Sensitivity analysis limited to patients with non-small cell lung cancer showed similar results (HR: 2.66 and 2.62, both p < 0.05). Moreover, subgroup analyses according to the diagnostic criteria of TRL, regression analysis model (univariate or multivariate), and indications of ICIs (for locally advanced or advanced lung cancer) showed consistent results (p for subgroup difference all > 0.05).ConclusionTRL was associated with poor survival of lung cancer patients who were treated with ICIs.

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Section: Discussionmentioning

confidence: 96%

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis

Zhang,

Huang,

2023

Front. Oncol.

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“…The same consideration applies to the absolute lymphocyte count, whose role has been extensively investigated in various cancers, including HNCs [ 32 , 37 ]. In our series, lymphocyte levels below 1000/mcl were associated with borderline significance with a lower LRPFS in the HPV-positive subgroup ( p = 0.084, results not shown).…”

Section: Discussionmentioning

confidence: 99%

Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit

Volpe

Gaeta

Colombo

et al. 2023

Cancers

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Aims: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. Methods: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models’ performance was compared by the C-index. Results: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52–66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5–7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80–0.84] for OS and 0.77 [CI: 0.75–0.79] for LRPFS. Conclusions: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.

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“…In support, pretreatment absolute lymphocyte count (<600 cells/μl) was significantly associated with response to PD-1 inhibitors in patients with head and neck squamous cell carcinomas (n=34) ( 140 ). In another study, lymphopenia (<1000 cells/μl) upon initiation of PD-1 inhibitor nivolumab was not associated with poorer survival in patients with head and neck squamous cell carcinomas (n=100), but persistent lymphopenia under nivolumab was associated with poorer overall survival in multivariate analysis (HR 3.96, 1.19-13.17, p=0.034) ( 141 ). Similarly, patients with metastatic melanoma (n=116) with a normal lymphocyte count at baseline but who developed lymphopenia during immune checkpoint inhibitor therapy had significantly shorter progression-free survival (13.3 versus 16.9 months, p=0.025) and overall survival (28.1 versus 36.8 months, p=0.01) compared with patients who did not develop ( 142 ).…”

Section: Standard Therapy-related Immunosuppression In Glioblastomamentioning

confidence: 99%

The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy

Stepanenko,

Sosnovtseva,

Valikhov

et al. 2024

Front. Immunol.

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Despite significant advances in our knowledge regarding the genetics and molecular biology of gliomas over the past two decades and hundreds of clinical trials, no effective therapeutic approach has been identified for adult patients with newly diagnosed glioblastoma, and overall survival remains dismal. Great hopes are now placed on combination immunotherapy. In clinical trials, immunotherapeutics are generally tested after standard therapy (radiation, temozolomide, and steroid dexamethasone) or concurrently with temozolomide and/or steroids. Only a minor subset of patients with progressive/recurrent glioblastoma have benefited from immunotherapies. In this review, we comprehensively discuss standard therapy-related systemic immunosuppression and lymphopenia, their prognostic significance, and the implications for immunotherapy/oncolytic virotherapy. The effectiveness of immunotherapy and oncolytic virotherapy (viro-immunotherapy) critically depends on the activity of the host immune cells. The absolute counts, ratios, and functional states of different circulating and tumor-infiltrating immune cell subsets determine the net immune fitness of patients with cancer and may have various effects on tumor progression, therapeutic response, and survival outcomes. Although different immunosuppressive mechanisms operate in patients with glioblastoma/gliomas at presentation, the immunological competence of patients may be significantly compromised by standard therapy, exacerbating tumor-related systemic immunosuppression. Standard therapy affects diverse immune cell subsets, including dendritic, CD4+, CD8+, natural killer (NK), NKT, macrophage, neutrophil, and myeloid-derived suppressor cell (MDSC). Systemic immunosuppression and lymphopenia limit the immune system’s ability to target glioblastoma. Changes in the standard therapy are required to increase the success of immunotherapies. Steroid use, high neutrophil-to-lymphocyte ratio (NLR), and low post-treatment total lymphocyte count (TLC) are significant prognostic factors for shorter survival in patients with glioblastoma in retrospective studies; however, these clinically relevant variables are rarely reported and correlated with response and survival in immunotherapy studies (e.g., immune checkpoint inhibitors, vaccines, and oncolytic viruses). Our analysis should help in the development of a more rational clinical trial design and decision-making regarding the treatment to potentially improve the efficacy of immunotherapy or oncolytic virotherapy.

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Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients

Cited by 7 publications

References 33 publications

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis

Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit

The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy

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