Abscopal-like Regression of Lung Metastases After Near-infrared Photoimmunotherapy Plus Nivolumab in Laryngeal Carcinoma

BACKGROUND/AIM: Near-infrared photoimmunotherapy (NIR-PIT) combines tumor-selective cytotoxicity with the induction of immunogenic cell death and may therefore augment the systemic activity of immune checkpoint inhibitors (ICIs). However, clinical evidence of responses in distant, non-illuminated lesions is lacking. We describe a distant visceral response following NIR-PIT administered during programmed cell death protein 1 (PD-1) blockade. CASE REPORT: A man in his 60s presented with recurrent laryngeal squamous cell carcinoma involving the base of the tongue and multiple pulmonary metastases that had progressed after definitive chemoradiotherapy, salvage total laryngectomy, re-irradiation, and platinum- and pembrolizumab-containing regimens. Nivolumab monotherapy was initiated, and NIR-PIT of the base-of-tongue lesion was added one month later. Using the pre-NIR-PIT status as baseline, the target pulmonary metastasis decreased from 12.1 to 8.0 mm and a cervical lymph node from 15.3 to 11.1 mm at 4 months (sum -30.3%; partial response by RECIST 1.1), with both lesions located outside the illuminated field. This response deepened and was maintained at 10 months (7.6 and 8.2 mm; sum -42.3%). In contrast, the illuminated base-of-tongue lesion persisted despite a second NIR-PIT at 5 months. Adverse events were limited to grade 2 facial and cervical edema and local pain. CONCLUSION: The addition of local NIR-PIT to nivolumab was followed by durable, abscopal-like regression of non-illuminated pulmonary metastases in immunotherapy-refractory head and neck cancer. While causality cannot be established from a single case, this observation supports formal investigation of NIR-PIT-ICI combinations in patients with distant metastases.