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Tumor mutational burden (TMB) is an emerging biomarker utilized in some cancers as a predictive tool to determine benefit to immune checkpoint inhibitor therapy and high TMB alone is an indication for pembrolizumab monotherapy, tumor agnostic. For head and neck squamous cell carcinoma (HNSCC), there is limited data utilizing TMB as a biomarker to predict response to PD-L1 inhibitors. This study assesses TMB score and progression of disease in HNSCC patients treated with immunotherapy. From an IRB-approved database, we retrospectively analyzed 51 patients treated between 2016 and 2023 with HNSCC who had at least one dose of pembrolizumab and known next generation sequencing (NGS). Patients were stratified between high TMB (≥10 mutations/Mb) and low (<10 mutations/Mb). Of the 51 patients, 40 (78%) had progression of disease while on pembrolizumab. The median TMB of those who progressed was 6.9 mutations/Mb. The median time to disease progression was 5.8 months. There were 37 patients who were classified as low TMB with a median 5.0 mutations/Mb. Of these 37, 29 (78%) had progression while on pembrolizumab with a median time to progression of 3.5 months. For the 14 patients with high TMB scores, the median was 12.0 mutations/Mb. Of these 14, 11 (79%) had progression while on pembrolizumab with a median time to progression of 5.8 months. There was no statistical difference in time to progression between high and low TMB cohorts (p=0.3483). Of the 11 (22%) without progression, all patients started pembrolizumab in the setting of recurrent HNSCC (7 metastatic, 4 locoregionally recurrent). The majority in this cohort are classified as having low TMB (n=8/11) with a median TMB of 5.0 mutations/Mb. Of the 10 patients who actively remain on pembrolizumab, they have been on pembrolizumab for a median of 14.7 months. A multivariable analysis revealed that TMB as a continuous variable (i.e., increase in TMB mutations), the risk of progression decreased (p=0.0238, HR 0.940). Although there was no statistical difference in time to progression between our high TMB and low TMB cohorts, a higher TMB score correlated with decreased risk of progression in our cohort of HNSCC patients. Further research is needed to better understand the utility of TMB as a biomarker in HNSCC. [ABSTRACT FROM AUTHOR]

Immunotherapy (IO) with cemiplimab or pembrolizumab is approved for treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC). There is evidence of objective response to these anti-PD-1 agents in locally advanced cSCC. Cranial nerve (CN) involvement is seen in less than 5% of cSCC and is a poor prognostic factor. Radiotherapy (RT) can be used for locally advanced cSCC, however comprehensive delineation and eradication of perineural invasion can be challenging. To our knowledge, there are no published studies indicating how patients with CN involvement respond to IO. Patients were identified and retrospectively reviewed under an Institutional Review Board approved protocol at a tertiary care center. Selection criteria included histologically proven locally advanced cSCC of the head and neck cancer with CN involvement treated with IO. A total of 8 patients met inclusion criteria; demographic, disease, and treatment characteristics are summarized in Table 1. Most patients were men, with a median age at diagnosis of 74 years and had a median follow-up of 8.4 months. All received cemiplimab 350 mg intravenously every 3 weeks; 1 patient was initially treated with pembrolizumab, then transitioned to cemiplimab. 2 patients received IO for recurrence of previously diagnosed locally advanced cSCC, 1 of which had prior treatment with cetuximab and RT. 6 patients presented with CN involvement at diagnosis, and the additional 2 at time of recurrence after previous non-IO therapy. 1 patient treated with IO was immunosuppressed due to CLL and also had nodal involvement. 4 patients received RT prior to IO, and 1 patient received stereotactic radiosurgery (SRS) concurrent with IO. 3 patients never received RT and all had clinical benefit with IO: 2 having stable disease (SD) and 1 partial response (PR). Overall, 4 patients had PR, 2 SD and 2 progressive disease (PD) as best response. 5 patients are alive at last follow up, 1 completed a full year of IO and is currently off treatment, and 4 remain on IO treatment. In this limited cohort of patients with locally advanced cSCC with CN involvement, IO has shown clinical benefit in 75% of the cases. All patients treated with IO alone demonstrated a clinical response, indicating IO can be an effective monotherapy. Given the challenges of RT with extensive perineural invasion, RT can be reserved in the event of local failure after IO. [ABSTRACT FROM AUTHOR]

Pembrolizumab and nivolumab are approved in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, real-world effectiveness may vary from clinical trial efficacy, partly due to strict exclusion criteria. We reviewed the effectiveness of immunotherapy (IO) in recurrent/metastatic HNSCC at a single tertiary referral center. All HNSCC patients who received single-agent palliative IO for recurrent/metastatic disease were identified from the electronic medical record via ICD codes under an IRB approved protocol. Wilcoxon rank sums test and chi squared test of independence were used to compare characteristics between IO responders (any response) and non-responders (stable or progressive disease) respectively. Kaplan-Meier method was used to estimate overall (OS) and progression free survival (PFS). Multivariable cox proportional hazards method was used to identify predictors of OS. A total of 138 patients were identified with the following primary tumor sites: p16+ oropharynx (n=45), p16- oropharynx (21), oral cavity (29), larynx (21), hypopharynx (7), nasal/sinus (7), or unknown primary (8). Concurrent chemoradiation was given to 68.8% (95) of patients and palliative chemotherapy was given prior to IO in 26.1% (36). IO was given for unresectable recurrent or metastatic disease in 23.2% (32) and 76.8% (106) of patients respectively, with 95.7% (132) receiving pembrolizumab and 4.3% (6) receiving nivolumab. Median age was 64 years (IQR 58-71), with ECOG status of 0, 1, and 2 in 23.9% (33), 60.9% (84), and 15.2% (21) of patients respectively. Combined positive scores (CPS) were available in 45.7% (63) of patients, with 33.3% (46) having CPS≥1 and 23.9% (33) having CPS≥20. The median number of IO cycles received was 4 (IQR 2-7). Of the 96 patients who survived to undergo imaging after ≥3 cycles, 43.8% (42) of patients had progression, 15.6% (15) had stable disease, 36.5% (35) had partial responses, and 4.2% (4) had complete responses. There were no significant differences in age, time from definitive radiation to IO, or absolute lymphocyte count (ALC) at IO initiation between responders and non-responders. Median PFS from IO initiation was 3.2 months (95%CI 2.8-4.4) months while median OS from IO initiation was 6.6 months (4.7-10.3). In a multivariable model, ECOG status of 1 (HR=2.00, 1.16-3.45) or 2 (HR=3.03, 1.51-6.09) vs ECOG 0 and decreased ALC at IO initiation (100 cells/µL, HR=1.06, 1.01-1.12) were significant predictors of worse OS. In this real-world cohort, survival with palliative IO in HNSCC was similar to that in randomized control trials. Though ECOG status and ALC were significant predictors of OS, further work into predictors of OS mediated through evidence of tumor response is needed. [ABSTRACT FROM AUTHOR]