Radium-223 alters the levels of soluble immune regulators in the plasma of patients with metastatic castrate-resistant prostate cancer.

Abstract

The approval of Radium 223 (Ra-223) has played an important role in the management of patients with metastatic castrate-resistant prostate cancer (mCRPC) by demonstrating improved symptom control and overall survival. However, not all patients respond, leading to an urgent need to develop combination therapies to improve patient outcome. Clinical studies investigating the efficacy of combining Ra-223 with immune checkpoint inhibitors (ICIs) have demonstrated limited success. A lack of understanding of how Ra-223 monotherapy alters immune regulators may play a role in the failure of these clinical studies. To address this knowledge gap, we collected plasma samples from patients with mCRPC treated with Ra-223 (n = 43) and aimed to first establish whether 61 relevant soluble immune regulators could be measured in patients with mCRPC and whether Ra-223 monotherapy modulates the expression of these regulators. Our study confirmed that soluble immune regulators can be detected in the plasma of patients with mCRPC and that Ra-223 significantly alters some of these regulators during treatment. Importantly, a differential response is observed in patients classified as non-responders and responders to Ra-223. With non-responders demonstrating treatment-induced changes in chemokines, matrix metalloproteinases and immune checkpoint molecules that occurred throughout the schedule. Whereas, in responders Ra-223 mostly induced early changes in cytokines, immune checkpoint and apoptotic cell clearance molecules. Our study provides much needed patient-derived data that can be further interrogated to better optimise Ra-223 and ICI combination treatment in these patients.