Ipilimumab and radiation therapy (RT) are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we performed a retrospective study reviewing records of patients treated with ipilimumab and RT for melanoma at our institution between 2005 and 2011. The review included details of treatment, response, adverse events (AEs), and overall survival (OS). Twenty-nine patients underwent 33 courses of non-brain RT between their first and last dose of ipilimumab. Immune-related AEs (ir-AEs) were observed in 43% of patients receiving ipilimumab at 10 mg/kg, and in 22% of patients receiving 3 mg/kg; the frequency of ir-AEs was not significantly different compared to previous studies of ipilimumab alone. RT-related AEs were significantly more common in patients receiving higher doses of radiation. Palliation of symptoms was reported by 77% of patients after RT. Median OS was 9 and 39 months in patients receiving RT during induction and maintenance with ipilimumab, respectively. In this retrospective study, concurrent ipilimumab and RT was not associated with higher than expected rates of AEs, nor did it abrogate palliative effects of RT or survival benefits of ipilimumab. Further studies to prospectively explore the efficacy of this therapeutic combination are warranted.

Highlights Arginine is a key nutrient shown to be essential in the life cycle of many viruses. SARS-CoV-2 replication relies on conserved arginine residues. Arginine depletion may also reduce inflammation in COVID-19 patients. Clinical stage arginine-depleting enzymes could be trialed in COVID-19 patients.

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