Arginine Deprivation for Malignant Pleural Mesothelioma

Arginine deprivation is a novel anticancer strategy in argininosuccinate synthetase 1 (ASS1)–negative tumors. In a multicenter, phase II trial, immunohistochemistry identified 68 patients with ASS1 deficiency among 201 patients with malignant pleural mesothelioma (MPM). The ASS1-deficient patients were randomized in a 2:1 ratio to either best supportive care (BSC) or BSC plus intramuscular ADI-PEG20, a pegylated arginine deiminase that causes arginine deprivation, at 36.8 mg/m² weekly (in 4-week cycles) for up to 6 months. Of the ADI-PEG20 recipients, 23% received six treatment cycles.

During a median follow-up of 38 months, no participants had partial or complete response. However, stable disease at 4 months (using modified Response Evaluat…