Anti-Tumor Immune Response by Combining Cryoablation and Transarterial Infusion of Pembrolizumab (CATAP) for Liver Metastases of Melanoma

Abstract

Background: Among patients with advanced stage melanoma receiving pembrolizumab, the presence of liver metastasis is an indicator suggestive of poor therapeutic response. A modified treatment strategy by combining transarterial infusion of pembrolizumab with cryoablation was proposed and its efficacy was assessed among this group of patients. Methods: This study retrospectively reviewed the records of 15 melanoma patients with multiple hepatic metastases who received a planned therapy of combined cryoablation with transarterial infusion of pembrolizumab (CATAP) in Sun Yat-sen University Cancer Center from Sep 1st 2018 to May 30th 2019. From 24th July, 2019 onward, the response rates and safety profile of this combination treatment were assessed prospectively with patient follow-up visits. Findings: The overall response rates (ORRs) of CATAP for the entire cohort, patients with primary cutaneous melanoma, with primary uveal melanoma, and patients who failed first-line intravenous pembrolizumab were 20.0%, 22.2%, 16.7%, and 16.7% respectively. The median time to response was 4.5 months and the median progress free survival (PFS) time in the cohort was 2.73 months. The estimated 6- and 12-month PFS rates were 31.0% and 18.6%, respectively, and the estimated 6- and 12-month overall survival (OS) rates were 73.9% and 49.3%, respectively. A significant increase of CD3-CD16+CD56+ cells (P = 0.0124) and a marginally significant decrease of CD4+CD25+ cells (P = 0.0546) were observed three weeks after the first cycle of CATAP therapy. No Grade 3-4 adverse events were observed. Interpretation: This study demonstrated a proof of concept that cryoablation can be safely combined with transarterial PD-1 blockade therapy and achieved synergistic anti-tumor immune response. Trial Registration: The Chinese Trial Register (ChiCTR) identifier was: ChiCTR1900024899. Funding Statement: This work was supported by grants from National Natural Science Foundation of China (No.81801804). Declaration of Interests: The authors indicate no financial relationships. Ethics Approval Statement: The Hospital Ethics Committee of SYSUCC approved this study (B2019-073-01), and patients with prospective follow up signed written informed consent.