Pembrolizumab induced remission of recurrent and metastatic sinonasal squamous cell carcinoma after overcoming checkpoint-inhibitor pneumonitis: A case report and literature review

Abstract

Background: For programmed death-ligand-1 (PD-L1) positive recurrent and metastatic head and neck squamous cell carcinoma (R/M-HNSCC), KEYNOTE-048 and KEYNOTE-040 clinical trials recently approved pembrolizumab monotherapy as first-line treatment. However, recurrent and metastatic sinonasal squamous cell carcinoma (R/M-SNSCC) was excluded from these clinical trials and treatment reports of immune-checkpoint inhibitor (ICI) in R/M-SNSCC are sparse. Immune-related adverse events (irAEs) are known to occur during ICI treatment and some of these such as checkpoint-inhibitor pneumonitis (CIP) can be fatal. ICI rechallenge after severe irAEs is debated.

Case: We describe a case of a 65-year-old male with R/M-SNSCC who is currently in remission with pembrolizumab monotherapy. He developed high-grade pneumonitis during the course of treatment warranting ICI discontinuation but has since tolerated full-dose pembrolizumab for 10 months now which is holding his disease stable. Our approach toward restarting full-dose pembrolizumab was by monitoring the patient's response to an initial low dose of pembrolizumab with concomitant oral steroid immunosuppression to control CIP.

Conclusion: Clinicians should weigh the risk-to-reward ratio of ICI rechallenge after improvement of high-grade CIP, particularly for selected patients with aggressive tumors such as R/M-SNSCC and prior treatment response. Under close monitoring, ICI resumption at a low dose and assessing patient tolerance with concomitant immunosuppression may be a reasonable approach to reintroducing ICI after high-grade CIP in these patients.

Keywords: checkpoint-inhibitor pneumonitis; immunotherapy; pembrolizumab; sinonasal squamous cell carcinoma.

FIGURE 1

Timeline of key events.

FIGURE 2

(A, B) PET/CT scan in February 2020: Hypermetabolic left posterior nasal cavity mass consistent with patient's known malignant tumor measuring 1.5 × 2.7 cm demonstrating a maximum SUV of 16.2 (blue, left arrow). Enlarged hypermetabolic left cervical level IIb lymph node consistent with regional metastasis measuring 1.8 × 2.2 cm with a maximum SUV of 15.6 (blue, up arrow). (C, D) PET/CT scan in October 2021: Hypermetabolic triangular shaped mass in the left posterior sidewall of the nasopharynx that appears to be decreased in size when compared to prior study; mass measures 1.1 × 2.2 cm with a maximum SUV of 8.9 (green, left arrow). Enlarged hypermetabolic left cervical level IIb lymph node identified on previous study is no longer present.

FIGURE 3

(A, B) CT scan in February 2021: Focal consolidative airspace disease in the posterior lateral right lower lobe and posterior basilar left lower lobe. Multifocal, peripheral ground‐glass opacities with round morphology more numerous in the right lung. Features are consistent with organizing pneumonia seen with drug toxicity. (C, D) CT scan in April 2021: Improved dense consolidation in the right lower lobe but the multiple small areas of focal consolidation within the right upper lobe on the previous examination have progressed since the previous study and there are also multiple new areas of focal irregular consolidation with central air bronchograms involving both lungs representing inflammatory process. (E, F) CT scan in October 2021: Diffuse ground‐glass infiltrates bilaterally in the lungs demonstrating mild metabolic activity with SUV of 2.2 concerning for unresolved pneumonitis.

FIGURE 4

Chest X‐ray in June 2021: Improved aeration of the lungs with decreasing peripheral based opacities, compared to CT chest done in April 2021, most notably in the right lung. No new focal consolidation, effusion, or pneumothorax.