Chemosaturation with percutaneous hepatic perfusion of melphalan for liver-dominant metastatic uveal melanoma: a single center experience

Abstract

Objective To investigate the outcome and safety data of chemosaturation with percutaneous hepatic perfusion (CS-PHP) of melphalan in patients with liver-dominant metastatic uveal melanoma. Material and methods This is a HIPAA compliant, IRB approved, retrospective study. A total of 28 CS-PHPs were performed in 16 individual patients (six men and ten women, median age 63.1 years [range 49.1 to 78.7 years], one to six CS-PHP procedures per patient) for treatment of liver-dominant metastatic uveal melanoma between June, 2015 and December, 2018. All patients received cross-sectional imaging at baseline and during follow-up. CS-PHP was performed with the Hepatic CHEMOSAT® Delivery System (Delcath Systems, Inc., NY, USA) facilitating extracorporeal filtration of hepatic blood for melphalan removal. Ideal body weight-adjusted melphalan doses were administered into the hepatic arteries. Serious adverse events (SAE), progression-free survival based on response criteria in solid tumors, and overall survival were noted. Survival data were analyzed using Kaplan-Meier estimates. Results Partial response after first CS-PHP was observed in nine patients (60%), stable disease in five patients (33%) and progressive disease in one patient (7%). Median overall survival was 27.4 months (95% CI 4.1 to 35.4 month) after first CS-PHP. Median progression-free survival was 11.1 months after first CS-PHP (95% CI 4.9 to 23.6 months). SAEs were observed in the majority of patients with most SAEs limited to grades one and two. Thirteen SAEs of grades three and four were observed in seven individual patients. No grade five SAE was observed. Conclusion CS-PHP is an efficacious and safe treatment for patients presenting with liver-dominant metastatic uveal melanoma.

Chemosaturation with percutaneous hepatic perfusion is effective in patients with ocular melanoma and cholangiocarcinoma

“…Hepatic injury, which manifested as transient increase of aminotransferases, was frequently seen following CS-PHP in accordance to the previous studies (Hughes et al 2016;Pingpank et al 2005;Meijer et al 2019;Artzner et al 2019;Kirstein et al 2017;Vogl et al 2014;Marquardt et al 2019). Hepatic dysfunction was less often observed with an overall rate of grade 3/4 hyperbilirubinemia of 15.3%.…”

“…The high crossover of BAC patients to CS-PHP confounded any possible overall survival advantage in this trial. A smaller retrospective study reported even longer survival times in patients with OM reaching up to 27 and 11 months for mOS and mPFS, respectively (Artzner et al 2019 ). However, these numbers might be overestimated due to the low number of patients ( n = 16) and procedures ( n = 28) in that study.…”

“…In the real-life setting, several retrospective studies have investigated the safety and efficacy of second-generation CS-PHP among various primary and secondary liver tumors—and most frequently in patients with OM (Artzner et al 2019 ; Kirstein et al 2017 ; Vogl et al 2014 ; Marquardt et al 2019 ). Patients with OM represent particularly eligible candidates for CS-PHP as these patients exclusively develop hepatic metastases, which are highly sensitive to melphalan (Feldman et al 2004a ; Jovanovic et al 2013 ).…”

“…In the real-life setting, several retrospective studies have investigated the safety and efficacy of CS-PHP among various secondary and primary liver tumors with promising results (Artzner et al 2019 ; Kirstein et al 2017 ; Vogl et al 2014 ). In patients with OM, mOS and median progression-free survival (mPFS) reached up to 27 and 11 months, respectively (Artzner et al 2019 ). Within our previous single-center experience, we have shown a good efficacy for patients with OM, but for patients with biliary tract cancer as well (Kirstein et al 2017 ).…”

Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan—Long-Term Overall Survival Negatively Correlates with Tumor Burden

“…Although evidence to date is limited, liver-targeted therapies such as PHP-M chemosaturation hold promising results for patients in this setting. However, the OS reported so far was within a large range from 245 days to 27 months [ 14 , 15 ], and data from randomized trials regarding long-term outcomes are not available.…”