Tumor Grade and Response to Immune Checkpoint Inhibition in Recurrent or Metastatic Mucosal HNSCC

Get Permission

In a single-institution retrospective cohort study reported in JAMA Otolaryngology–Head & Neck Surgery, Alkhatib et al found a higher rate of response to immune checkpoint inhibitor treatment among patients with histologic high-grade vs low-grade recurrent or metastatic mucosal head and neck squamous cell carcinoma (HNSCC).

Study Details

The study involved data from 60 patients treated with immune checkpoint inhibitors at Johns Hopkins Hospital between July 2015 and January 2020. A total of 35 had high-grade tumors and 25 had low-grade tumors; the oropharynx was the most common primary tumor site in both groups (n = 22 and n = 12, respectively). The primary outcome measure was clinically beneficial immunotherapy response, defined as complete or partial response on Response Evaluation Criteria in Solid Tumors version 1.1.

Key Findings

A clinically beneficial response was observed in 12 (34.3%) of 35 patients with high-grade tumors vs 2 (8.0%) of 25 with low-grade tumors (difference = 26.3%, 95% confidence interval [CI] = 7.3%–45.3%). On multivariate analysis, high-grade tumor status was a significant predictor of beneficial response (odds ratio = 5.35, 95% CI = 1.04–27.37). No significant association with response was observed for age; sex; primary tumor site; human papillomavirus status; smoking history; T-stage; total number of metastases; or the presence of lung, bone, or liver metastasis.  

Among eight patients with high-grade tumors and four with low-grade tumors with available tumor genomic profiling data, the mean tumor mutational burden was higher in the high-grade group (8.6 vs 3.6 mut/Mb; difference = 5.0 mut/Mb, 95% CI = −1.4 to 11.4 mut/Mb).

Among 33 vs 23 patients with available survival follow-up, median progression-free survival was 5.9 months (95% CI = 3.8–11.1 months) in the high-grade group vs 3.3 months (95% CI = 1.7–4.7 months) in the low-grade group (adjusted hazard ratio [HR] = 0.69, 95% CI = 0.39–1.22). Median overall survival was 16.6 months (95% CI = 11.1–25.0 months) vs 15.0 months (95% CI = 8.2–22.8 months; adjusted HR = 0.94, 95% CI = 0.47–1.89).

The investigators concluded, “In this cohort study, tumor grade was independently associated with immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. These findings highlight the potential role of tumor grade in predicting immunotherapy response in mucosal HNSCC.”

Rajarsi Mandal, MD, of the Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, is the corresponding author for the JAMA Otolaryngology-Head & Neck Surgery article.

Disclosure: For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.