Atypical new metastatic sites after immunotherapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M H&NSCC)

e18032 Background: Immunotherapy with PD-1 inhibitors (PD-1Is) nivolumab (N) or pembrolizumab (P) has led to significant improvements in overall survival in pts with R/M H&NSCC. Common metastatic (met) sites for R/M H&NSCC are locoregional in the H&N area (LR), lung (L) and liver (LV). We investigated where patients developed met sites after successful treatment with PD-1Is. Methods: Eligible pts were treated with N or P for at least 3 months in the 1 st or 2 nd line setting and with at least stable disease as best response. Records were reviewed for initial sites of disease and whether metastatic sites developed after PD-1 therapies, including during subsequent lines of therapy. Patients could have more than one initial or progressive metastatic/recurrent sites of disease. Results: 26 eligible pts treated between 2016-2022 were identified with demographics as follows: 20 males/6 females; average age 65.3 yrs; primary diseases were 13 oropharynx (12 HPV+), 10 oral cavity, 1 larynx, and 2 nasopharynx; 8 received N and 18 got P (4 with chemotherapy); 22 were treated in 1 st line and 4 in 2 nd line. The median time on PD-1I therapy was 51.7 weeks (range 19 – 100). Best response was stable disease in 9 (35%), partial response in 15 (58%), and complete response in 2 (8%). Initial sites of disease were: LR 16 (62%), L 16 (62%), LV 2 (8%) and bone 2 (8%). In the 16 pts who developed new sites of disease, these included L in 5 (31%), LV in 4 (25%), bone in 7 (44%), abdomen/mesentery in 7 (44%), lower extremities in 4 (25%), and brain in 3 (19%). All 3 who developed CNS mets had HPV+ oropharynx cancer. Conclusions: Pts successfully treated with PD-1Is had uncommon sites of new metastatic disease, including in the lower extremities, abdomen, and brain. This has important ramifications for restaging scan requirements in these patients while on treatment. These results also raise the possibility of disease site sanctuaries resistant to immunotherapy, including in the abdomen, bone, and brain. Larger patient series should be investigated.