2016 - High Immunoscore is associated with good response to neo-adjuvant chemotherapy and prolonged survival in advanced Head and Neck cancer patients.

Background

The presence of high levels of tumor immune infiltrate has been recognized to be associated with better prognosis in Head and Neck cancer (H&N). The consensus Immunoscore quantifies the densities of CD3 and CD8 in the center of the tumour (CT) and the invasive margin (IM) and stratifies patients into 3 Immunoscore categories (Low, Intermediate and High).

Methods

This retrospective ongoing study evaluated the Immunoscore in 110 patients with advanced laryngeal (n = 57) or hypopharyngeal (n = 53) cancers who received neo-adjuvant chemotherapy in the setting of an organ preservation protocol. Good responders (tumor reduction > 50%) were subsequently treated by radiation/chemoradiation, whereas non-responders were subjected to surgery followed by post-operative radiation/chemoradiation. Pre-treatment tumor samples were immune-stained for T-cell (CD3, CD8) markers and quantitative analysis of the immune cells was carried out in different tumor locations using a computer-assisted image analysis.

Results

60% of patients were good responders. Densities of T cell infiltration were significantly higher for Hypopharyngeal cancer patients compared to those with laryngeal cancer. ( P < 0.001) Analysis of the entire cohort showed that good-responders had a higher Immunoscore than non-responders (69% vs. 39%% respectively, Odd Ratio = 2.7303 CI 95%[0.8497-9.24], P = 0.069). Immunoscore Low, Intermediate and High represented respectively 16.5%, 45.6% and 37.9% of the cohort. High Immunoscore patients were at low risk of relapse, with 5-year Time to Recurrence rates of 71.4 (CI 53.9 − 94.6) as compared to 54.6 CI 95% (40.4 − 73.9) and 31.4 CI 95% (13.3 − 74.1) in intermediate and low Immunoscore patients respectively (HR = 1.9 CI 95% (1.2 − 3.0), P < 0.02). Similar results were found in Larynx and Hypopharynx separately. Regardless of treatment type and tumor location, a high Immunoscore was associated with better progression-free survival and overall survival.Table: 1115PD

CPS, combined positive score; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; SOC, standard of care; TPS, tumor proportion score.

Sensitivity, specificity, N (prevalence), and ORR are for the pembrolizumab arm. Odds ratio, PFS HR, and OS HR compare pembrolizumab and SOC.

Conclusions

The results of this ongoing study show a significant prognostic and potentially predictive role of Immunoscore in H&N cancer patients with important therapeutic implications.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Haitham Mirghani.

Funding

HalioDx.

Disclosure

H. Mirghani: Advisory / Consultancy: MSD vaccin; Travel / Accommodation / Expenses: BMS. B. Mlecnik: Licensing / Royalties: HalioDx. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: HalioDx. C. Even: Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: Innate Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca. J. Galon: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: HalioDx; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Merck Serono; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Sanofi; Honoraria (self): Gilead; Advisory / Consultancy, Research grant / Funding (institution): IOBiotech; Advisory / Consultancy: Illumina; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Actelion; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Perkin-Helmer; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Imcheck; Licensing / Royalties: Inserm. All other authors have declared no conflicts of interest.