Immunotherapy Response in Patients with Pre-Existing Autoimmune Disorders and Head and Neck Cancers

Abstract

<h3>Purpose/Objective(s)</h3> Immune checkpoint inhibitors (ICIs) offer clinical benefit in a subset of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and are complicated by immune-related adverse events (irAEs). Patients with pre-existing autoimmune disorders (AID) are generally excluded from clinical trials due to concern for irAEs. Studies of AID patients on ICIs have been completed in melanoma and NSCLC, but limited in HNSCC. Here, we compare characteristics, outcomes, and toxicities of HNSCC patients with and without AIDs to better understand the safety and efficacy of ICIs in this cohort. <h3>Materials/Methods</h3> Retrospective data was collected from HNSCC patients who received anti-PD1/PD-L1 monotherapy or combination therapy at our institution between Jan. 2015 and Dec. 2018 following IRB approval. Baseline characteristics, genomic data, and ICI response were collected. Data concerning AID diagnosed prior to ICI start, AID activity, ICI toxicity (flare of AID/irAE), and their treatment were also collected. Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response to ICIs was based on Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Survival was estimated using the Kaplan-Meier method, and Cox proportional hazards regression was used with toxicity as a time-dependent covariate. <h3>Results</h3> 76 HNSCC patients who received ICIs were identified, 6 with pre-existing AID (7.9%). There were no significant differences between non-AID and AID cohorts, including in age, gender, tumor mutational burden, or neutrophil-to-lymphocyte ratio. ICI response rates were 22.9% in the non-AID and 16.7% in the AID group (p=1.000). No differences were seen in progression-free survival (PFS) and overall survival (OS) (p=.664, p=.747). In the AID cohort, observed AID were psoriasis (n=3), lichen planus (n=2), and inflammatory bowel disease (IBD) (n=1). No patients were receiving systemic immunosuppression at ICI start; 2 were on topical steroid for psoriasis. All patients received anti-PD1 therapy (pembrolizumab=2; nivolumab=4), with a mean treatment time of 423 days. Toxicity was recorded in 3/6 AID patients, 2 with AID flare and 1 with new irAE. Mild flares (CTCAE 1-2) were observed in patients with IBD and lichen planus. Lichen planus flare was treated with topical steroid, and IBD flare with high-dose prednisone and discontinuation of ICI. 1 patient with AID of psoriasis demonstrated irAE of hypothyroidism treated with levothyroxine. There were no significant differences in response, OS, or PFS between AID patients who did and did not experience toxicity (p=1.000, p=.646, p=.150). <h3>Conclusion</h3> Our data suggests that the efficacy of ICIs in patients with HNSCC and AIDs are similar to patients without AIDs. Patients with AIDs with HNSCC experience toxicity at similar rates to those described in other cancer types.