Abscopal effect observed in visceral and osseous metastases after liver SBRT in combination with nivolumab and relatlimab for sinonasal mucosal melanoma-a case report.

Background: Primary sinonasal mucosal melanoma (SNMM) is a rare, aggressive histology usually diagnosed at advanced stages and associated with poor prognosis. Evidence regarding etiology, diagnosis, and treatment mainly derives from case reports, retrospective series, and national databases. In the treatment of metastatic melanoma, anti-CTLA-4 and anti-PD-1 checkpoint blockade increased 5-year overall survival from ~10% (prior to 2011) to ~50% (between 2011 and 2016). In March of 2022, the FDA approved the use of relatlimab, a novel anti-LAG3 immune checkpoint inhibitor, for the treatment of melanoma. Case presentation: A 67-year-old woman with locally advanced SNMM underwent debulking surgery, adjuvant RT, and first-line immunotherapy (ImT) with nivolumab but developed local progression. The patient started a second course of ImT with nivolumab and ipilimumab, but this was discontinued after two cycles due to an immune-related adverse event (irAE, hepatitis with elevated liver enzymes). Interval imaging identified visceral and osseous metastases including multiple lesions in the liver and in the lumbar spine. She went on to receive a third course of ImT with nivolumab and the novel agent relatlimab with concurrent stereotactic body radiation therapy (SBRT) to the largest liver tumor only, delivered in five 10-Gy fractions using MRI guidance. A PET/CT performed 3 months after SBRT demonstrated complete metabolic response (CMR) of all disease sites including non-irradiated liver lesions and spinal metastatic sites. After two cycles of the third course of ImT, the patient developed severe immune-related keratoconjunctivitis and ImT was discontinued. Conclusion: This case report describes the first complete abscopal response (AR) in an SNMM histology and the first report of AR following liver SBRT with the use of relatlimab/nivolumab combination ImT for metastatic melanoma in the setting of both visceral and osseous lesions. This report suggests that the combination of SBRT with ImT potentiates the adaptive immune response and is a viable path for immune-mediated tumor rejection. The mechanisms behind this response are hypothesis-generating and remain an area of active research with exceedingly promising potential.