Sep 28

SS 15 - Immunotherapy Integration and Immuno Biomarkers Across Mucosal and Cutaneous SCC

174 - Secondary Immunological Analysis of a Prospective Trial in Patients with Recurrent Head and Neck Malignancies

11:05am - 11:15am ET

Room 107

Presenter(s)

Soumya Unnikrishnan, MD, MS - Winship Cancer Institute of Emory University, Atlanta, GA

S. Unnikrishnan¹, E. Connolly², T. Clark³, J. Dooyema³, N. F. Saba⁴, H. T. Kissick⁵, N. C. Schmitt⁶, C. Lee-Poturalski⁷, T. A. Chan⁸, D. S. Yu⁹, and Z. S. Buchwald¹; ¹Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ²Winship Cancer Institute of Emory University, Atlanta, GA, ³Emory University School of Medicine, Atlanta, GA, ⁴Emory University, Atlanta, GA, ⁵Department of Urology, Emory University, Atlanta, GA, ⁶Department of Otolaryngology, Winship Cancer Institute of Emory University, Atlanta, GA, ⁷Cleveland Clinic, Cleveland, OH, ⁸Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, ⁹Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA

Purpose/Objective(s):

Re-irradiation (RT) and anti-PD1 are both used commonly in recurrent or second primary head and neck squamous cell carcinoma (HNSCC) with sub-optimal clinical outcomes. Anti-PD1 exerts its effects through stimulation of progenitor CD8+ PD1+ TCF1+ T cells maintained within specialized intratumoral niches that act as reservoirs for T cell reinvigoration. RT may modulate these niches by promoting local inflammation and enhancing CD8 T cell stimulation.

Materials/Methods:

This is a secondary analysis of data from a previously published multi-institutional Phase 2 single-arm clinical trial evaluating concurrent intensity-modulated radiation therapy (IMRT) and Nivolumab in recurrent or second primary HNSCC (Saba et al, JAMA Oncol 2024). In our study, tumor tissue collected pre-treatment was analyzed using multi-parametric immunofluorescence and spatial computational analysis. Single cell marker intensities and coordinates were used to phenotype immune populations, and spatial density maps were generated to define immune niches based on co-localization of CD8+PD1+TCF1+ T cells and MHC-II+ cells, which were then correlated with clinical outcomes. Kaplan Meier Estimate was used to calculate progression-free and overall survival (PFS, OS). The optimal cutoff values for each immune correlate were determined by log-rank tests to dichotomize patients into “high” and “low” groups for intergroup comparisons.

Results:

30 patients with pre-treatment tumor tissue available were analyzed. The median age was 59 years. 25 (83%) were males. 18 (59%) had oral cavity or oropharyngeal primaries. 16 (53%) had Combined Positive Score (CPS) <20. The median PFS and OS were 9.4 and 15.7 months (mo) respectively. No patients with “high” CD8% showed progression, whereas the median PFS in the “low” group was 14.2 mo (p= 0.019). A trend towards improved median PFS was noted in the “high” CD4% group (27.1 mo) vs “low” group (8 mo) (p= 0.060); similarly, “high” CD8+PD1+ density trended towards better PFS (27.1 mo) vs “low” (14.2 mo) (p= 0.111). Patients in the “high” group demonstrated better OS compared to their counterparts in the “low” group for CD8+ density (median 27.1 and 15.1 mo, p= 0.037), as well as CD8+ PD1+ density (median 27.1 and 16 mo, p=0.049). Additionally, patients in the “high” and “low” groups for niche density % had median OS of 30.6 and 16 mo respectively (p= 0.035). CD8+PD1+TCF1+ density also showed a trend towards improved median OS of 27.1 mo in the “high” group versus 14.2 mo in the “low” group (p= 0.100).

Conclusion:

Immunological characteristics of the baseline tumor microenvironment such as absolute T cell infiltration, differentiation state and spatial organization may serve as predictive biomarkers of survival in patients with recurrent and second primary head and neck malignancies treated with re-irradiation and anti-PD1 and may aid in selection of patients expected to have improved clinical outcomes from this treatment paradigm. (NCT03521570)