Percutaneous Hepatic Perfusion Research Articles

Hepatic and Overall Progression-Free Survival After Percutaneous Hepatic Perfusion (PHP) as First-Line or Second-Line Therapy for Metastatic Uveal Melanoma.

Uveal melanoma often metastasizes to the liver, portending a poor prognosis. Melphalan/hepatic delivery system (HDS) via percutaneous hepatic perfusion (PHP) is a minimally invasive means of circulating high-dose chemotherapy through the affected liver. This study evaluated melphalan/HDS use as either first-line or second-line treatment to guide treatment sequencing. A retrospective review included patients with hepatic-dominant metastatic uveal melanoma who underwent melphalan/HDS treatment via PHP from 2008 to 2023. A total of 30 patients were identified; 53.3% female, with a median age of 63.5 years (37-78 years). Median follow-up time was 14.5 months. First-line therapies included melphalan/HDS (n = 17), liver-directed (n = 7), and immunotherapy (n = 6). Second-line therapies included melphalan/HDS (n = 6), immunotherapy (n = 5), and liver-directed (n = 3). Median hepatic progression-free survival (hPFS) for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 17.6/8.8/9.2 months, respectively (P = 0.002). Median hPFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was not reached/14.7/7.5 months, respectively (P < 0.001). Median overall PFS for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 15.4/8.8/9.2 months, respectively (P = 0.04). Median overall PFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was 22.2/14.7/7.5 months, respectively (P = 0.001). Melphalan/HDS via PHP for metastatic uveal melanoma to the liver was found to have significantly improved hPFS and overall PFS when used as first-line therapy compared with immunotherapy or liver-directed therapy. PHP continued to demonstrate improved hPFS and PFS when used as second-line therapy compared with second-line immunotherapy or liver-directed therapy.

72215 - Percutaneous hepatic perfusion as treatment for liver-dominant metastatic uveal melanoma: the first results from a Nordic referral center

72215 - Percutaneous hepatic perfusion as treatment for liver-dominant metastatic uveal melanoma: the first results from a Nordic referral center

First-line therapy for metastatic uveal melanoma: Experience from a single reference center.

e21514 Background: Metastatic uveal melanoma (mUM) continues to have a poor prognosis with distinct biology from cutaneous melanoma and limited effective treatment options. The main options include immunotherapy (IT, anti-PD-1+/- anti-CTLA-4, tebentafusp), chemotherapy, targeted therapy and local treatment methods for patients with isolated liver metastasis (isolated hepatic perfusion, transarterial chemoembolization, percutaneous hepatic perfusion, radiofrequency ablation). Methods: We conducted a single-center retrospective observation IRB-approved study of first-line therapy for pts age 18 and older with mUM treated at the N.N. Blokhin National Medical Research Center of Oncology from 2020 to 2023. Our objectives were to evaluate clinical outcomes in real-world settings, as well as treatment patterns, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 125 pts included. The mean age was 54 yrs (range: 20-74), and the median time to metastasis from primary tumor was 2 years (range: 0-21). Liver metastases were diagnosed in 92% of patients, lung metastases in 20%, bone metastases in 17%, and soft tissue metastases in 9%. Conclusions: Our data suggest that the combination of systemic and local liver-directed treatment methods may be associated with a survival benefit and higher treatment response to IT in patients with mUM. [Table: see text]

Intralesional and Infusional Updates for Metastatic Melanoma.

Locoregionally advanced and metastatic melanoma represent a challenging clinical problem, but in the era of immune checkpoint blockade and intralesional and infusional therapies, more options are available for use. Isolated limb infusion (ILI) was first introduced in the 1990s for the management of advanced melanoma, followed by the utilization of isolated extremity perfusion (ILP). Following this, intralesional oncolytic viruses, xanthene dyes, and cytokines were introduced for the management of in-transit metastases as well as unresectable, advanced melanoma. In 2015, the Food and Drug Administration (FDA) approved the first oncolytic intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of advanced melanoma. Additionally, immune checkpoint inhibition has demonstrated efficacy in the management of advanced melanomas, and this improvement in outcomes has been extrapolated to aid in the management of in-transit metastatic disease. Finally, percutaneous hepatic perfusion (PHP), also approved by the FDA, has been reported to have a significant impact on the treatment of hepatic disease in uveal melanoma. While some of these treatments have less utility due to inferior outcomes as well as higher toxicity profiles, there are selective patient profiles for which these therapies carry a role. This review highlights intralesional and infusional therapies for the management of metastatic melanoma.

ASO Author Reflections: Percutaneous Hepatic Perfusion: Past, Present, and Future.

ASO Author Reflections: Percutaneous Hepatic Perfusion: Past, Present, and Future.

Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases

PurposePercutaneous hepatic perfusion with melphalan (M-PHP) is a minimally invasive therapy with proven efficacy in patients with uveal melanoma (UM) liver metastases. M-PHP is associated with a short hospital admission time and limited systemic side effects. In this study, we assessed quality of life (QoL) in UM patients treated with M-PHP.Materials and MethodsA prospective, single-center study including 24 patients treated with M-PHP for UM metastases to the liver. QoL questionnaires were collected at baseline, on day 2/3 after M-PHP, and on day 7 and day 21 after M-PHP, according to study protocol. The results were scored according to EORTC-QLQ C30 global health status (GHS), functional scales, and symptom scales. The difference in scores at baseline and subsequent time points was analyzed with the Wilcoxon signed-rank test and multiple testing Bonferroni correction. Adverse events (AE) were registered up to 30 days after M-PHP according to CTCAE v5.0.ResultsTwenty-four patients (14 males; median age 63.0 years) completed 96 questionnaires. Most scores on all scales declined on day 2/3 after M-PHP. On day 21 after M-PHP, 12 out of 15 scores returned to baseline, including median GHS scores. Three variables were significantly worse on day 21 compared to baseline: fatigue (6–33; p = 0.002), physical functioning (100 vs 86.7; p = 0.003), and role functioning (100 vs 66.7; p = 0.001). Grade 3/4 AEs consisted mainly of hematological complications, such as leukopenia and thrombopenia.ConclusionM-PHP causes fatigue and a decline in physical and role functioning in the 1st weeks after treatment, but GHS returns to baseline levels within 21 days.Level of Evidence 3Cohort study.Graphical

The role of percutaneous hepatic perfusion (PHP) in the treatment of cholangiocarcinoma

This review article evaluates the current literature on the role of percutaneous hepatic perfusion (PHP) as a treatment option in cholangiocarcinoma (CCA). CCA is a rare cancer that is mostly diagnosed at a late stage. Patients with advanced, unresectable disease have limited treatment options. PHP is a locoregional therapy that delivers high doses of chemotherapy directly to the liver while minimizing systemic exposure and toxicity. This review allocates PHP in the therapeutic spectrum of CCA and summarizes the available literature with a focus on the clinical efficacy and safety profile. Results from studies evaluating the efficacy and safety of PHP are promising, with several observational studies demonstrating improvements in progression-free survival and overall survival rates. However, PHP is not without side effects; the most commonly reported adverse events include transient hematotoxicity and hepatotoxicity. PHP has the potential to be a valuable treatment option for patients with unresectable CCA. Nonetheless, further trials are needed to optimize patient selection, treatment regimens, and long-term outcomes.

Troponin Elevation in Patients Undergoing Percutaneous Hepatic Perfusion for Metastatic Uveal Melanoma.

Percutaneous Hepatic Perfusion (PHP) is a liver directed regional therapy recently FDA approved for metastatic uveal melanoma to the liver involving percutaneous isolation of liver, saturation of the entire liver with high-dose chemotherapy and filtration extracorporeally though in line filters and veno-venous bypass. The procedure is associated with hemodynamic shifts requiring hemodynamic support and blood product resuscitation due to coagulopathy. To assess the cardiac safety and subsequent clinically significant sequalae of this therapy. Consecutive PHP procedures done at our center between 2010-2022 were assessed retrospectively. Cardiac risk factors, post procedural cardiac enzymes, electrocardiograms, and transthoracic echocardiograms along with 90-day cardiac outcomes were reviewed. All data were reviewed by cardio-oncologists at our institution. Of 37 patients reviewed, mean age was 63years and 57% were women. 132 procedures were performed with an average of 3.57 procedures per patient. 68.6% of patients had elevated troponin during at least 1 procedure. No patients were found to have acute coronary syndrome, heart failure, unstable arrhythmias, or cardiac death. No patients had notable echocardiographic changes. 10.8% of patients with positive troponin had asymptomatic transient electrocardiographic changes not meeting criteria for myocardial infarction. One patient had non-sustained ventricular tachycardiac intra-operatively which did not recur subsequently. Three patients died from non-cardiac causes within 90-days. There was no oncology treatment interruption, even in those with troponin elevation. In multivariable analysis, a history of hyperlipidemia was a predictor of postoperative troponin elevation. (P = .042). Percutaneous Hepatic Perfusion is safe and associated with a transient, asymptomatic troponin elevation peri-operatively without major adverse cardiac events at 90days. The observed troponin elevation is likely secondary to coronary demand-supply mismatch related to procedural hemodynamic shifts, hypotension, and anemia.

Quality of life after melphalan percutaneous hepatic perfusion for patients with metastatic uveal melanoma.

Recent studies indicate that melphalan percutaneous hepatic perfusion (M-PHP) for liver metastases from ocular melanoma (mUM) improves survival. Importantly, this benefit must be carefully balanced with changes in a patient's quality of life (QoL). This study examines the QoL changes post-M-PHP. Retrospective analysis of the change in QoL using the Functional Assessment of Cancer Therapy-General (FACT-G) with mUM patients receiving M-PHP ( n = 20). The FACT-G scores, which comprise physical (PWB), social (SWB), emotional (EWB) and functional (FWB) wellbeing were measured pre-procedure and at day 1, day of discharge (mean = 2.4 days), 7, 14 and 28 days after M-PHP therapy. Wilcoxon signed-rank test gauged QoL domain changes. Baseline FACT-G median (IQR) scores were 101.8 (21.8). QoL scoring significantly decreased immediately after the procedure [day 1; 85 (27.5); P = 0.002] and gradually improved over time. By day 28, QoL almost returned to pre-procedure levels [100.3 (13.8); P = 0.31]. Subscore analysis revealed that the initial drop in QoL at day 1 post-procedure was attributable to the PWB (28 vs. 24; P = 0.001) and FWB domains (26 vs. 18.5; P < 0.001). By day 28 there was a statistically significant improvement in EWB ( P = 0.01). QoL following M-PHP decreases immediately after therapy and is not significantly different from baseline by the day of discharge. By day 28 there is improved emotional well-being. This study could help to optimize the time between treatment cycles when combined with toxicity data and blood count recovery.

Prognostic Factors for Postoperative Bleeding Complications and Prolonged Intensive Care after Percutaneous Hepatic Chemosaturation Procedures with Melphalan.

Percutaneous hepatic melphalan perfusion (chemosaturation) in patients with liver metastases is known to be associated with procedure-related hemodynamic depression and coagulation impairment, which may cause bleeding complications and/or a prolonged intensive care unit length of stay (ICU LOS). We retrospectively analyzed possible predictive factors for bleeding complications and an ICU LOS > 1 d in a cohort of 31 patients undergoing 90 chemosaturation procedures. Using a multivariable mixed-model approach, we identified the amount of perioperative fluid volume (OR 12.0, 95% CI 2.3-60.0, p = 0.003) and protamine (OR 0.065, 95% CI 0.007-0.55, p = 0.012) to be associated with bleeding complications. Furthermore, the amount of perioperative fluid volume was associated with an ICU LOS > 1 d (OR 5.2, 95% CI 1.4-19.0, p = 0.011). Heparin dosage, melphalan dosage, extracorporeal circulation time, and noradrenaline dosage had no significant effects on outcomes. Protamine use was not associated with anaphylactic or thromboembolic complications. Despite the limited sample size, these results suggest a restrictive perioperative fluid regime to be beneficial, and support the use of protamine for heparin reversal after chemosaturation procedures. Further prospective randomized trials are needed to confirm these findings.

Heparin reversal with protamine sulfate after Percutaneous Hepatic Perfusion (PHP): is less more?

PurposePercutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP.Materials and methodsAll patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (groupPROTAMINE); 13 patients/21 PHP in groupREDUCED_PROTAMINE received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (groupNO_PROTAMINE). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0).ResultsThromboembolic events were recorded after 10 PHP procedures (5%) in groupPROTAMINE, six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in groupREDUCED_PROTAMINE and groupNO_PROTAMINE. Hemorrhagic events were registered after 24 PHP (13%) in groupPROTAMINE, two of which (1%) were major (CTCAE grade 3-4). In groupREDUCED_PROTAMINE, only minor bleeding events were recorded, and one major hemorrhagic event was documented in groupNO_PROTAMINE (2%). There was a significant difference between the percentage of post-interventional thrombopenia in groupPROTAMINE (39%) and groupREDUCED_PROTAMINE (14%) versus groupNO_PROTAMINE (23%) (p=.00024). In groupPROTAMINE one patient suffered from a severe anaphylactic shock after the administration of protamine.ConclusionOur retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated.

Minimally Invasive Treatment Options for Hepatic Uveal Melanoma Metastases.

Uveal melanoma is one of the most common primary intraocular malignancies that accounts for about 85% of all ocular melanomas. The pathophysiology of uveal melanoma is distinct from cutaneous melanoma and has separate tumor profiles. The management of uveal melanoma is largely dependent on the presence of metastases, which confers a poor prognosis with a one-year survival reaching only 15%. Although a better understanding of tumor biology has led to the development of novel pharmacologic agents, there is increasing demand for minimally invasive management of hepatic uveal melanoma metastases. Multiple studies have already summarized the systemic therapeutic options available for metastatic uveal melanoma. This review covers the current research for the most prevalent locoregional treatment options for metastatic uveal melanoma including percutaneous hepatic perfusion, immunoembolization, chemoembolization, thermal ablation, and radioembolization.

Anesthesiological and postinterventional management in percutaneous hepatic melphalan perfusion (chemosaturation)

Percutaneous hepatic melphalan perfusion (PHMP) is alast-line treatment of inoperable primary or secondary liver tumors. Selective perfusion and saturation (chemosaturation) of the liver with the chemotherapeutic agent melphalan is performed via catheterization of the hepatic artery without affecting the rest of the body with its cytotoxic properties. Using an extracorporeal circulation and balloon occlusion of the inferior vena cava, the venous hepatic blood is filtered and returned using abypass procedure. During the procedure, considerable circulatory depression and coagulopathy are frequent. The purpose of this article is to review the anesthesiological and postprocedural management of patients undergoing PHMP with consideration of the pitfalls and special circumstances.

New perspectives in unresectable cholangiocarcinoma? Evaluation of chemosaturation with percutaneous hepatic perfusion as a palliative treatment option

Cholangiocarcinoma (CCA) are the second most common primary liver tumors and carry a dismal prognosis. Chemosaturation with percutaneous hepatic perfusion (PHP) is a palliative, intra-arterial therapeutic approach that provides a high dose chemotherapy of the liver with reduced systemic exposure. Aim of this retrospective, monocentric study was to analyze PHP as a palliative treatment for unresectable CCA. Toxicity, adverse events and complications were classified using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic mPFS (mhPFS) were computed using Kaplan–Meier estimation. In total 17 patients were treated with 42 PHP between 10/2014 and 09/2020. No significant complications occurred during the interventions. mOS was 27.6 (interquartile range (IQR) 16.5–37) months from first diagnosis and 9.9 (IQR 3.8–21) months from first PHP. mPFS was 4 (IQR 2–7) and mhPFS was 4 (IQR 3–10) months. ORR was 25% and DCR 75%. Significant, but transient hematotoxicity was frequent with grade 3/4 thrombopenia after 50%, leukopenia after 26% and anaemia after 21% of the interventions. An increase of transaminases (AST increase after 21% and ALT increase after 14% of the PHP) developed more often than a deterioration of the liver synthesis capacity. Salvage treatment with PHP has the potential to prolong life in selected patients with unresectable, refractory cholangiocarcinoma. The interventional procedure is safe. Post-interventional toxicity is frequent but manageable.

Chemosaturation of the Liver - an Update.

Percutaneous hepatic perfusion (CS-PHP) is a treatment option for primary and secondary liver neoplasms and subject of intensive research. This present article provides an overview of CS-PHP regarding patient safety, feasibility and effectiveness based on recent studies. We performed a PubMed search including the search terms chemosaturation, hepatic chemosaturation, percutaneous perfusion and melphalan. CS-PHP is a promising procedure for the treatment of uveal melanoma and cholangiocellular carcinoma. There are insufficient data regarding the effectiveness of CS-PHP with respect to other tumor entities. Since CS-PHP can be accompanied by multiple transient side effects and complications, close interdisciplinary cooperation is necessary. · Chemosaturation of the liver is a safe procedure.. · CS-PHP is a potent therapy for hepatic metastatic ocular melanoma and cholangiocellular carcinoma.. · The procedure requires close interdisciplinary coordination.. · CS-PHP is a repeatable and thus long-term therapeutic option for some patients.. · Ebel S, Struck MF, van Boemmel F et al. Chemosaturation of the Liver - an Update. Fortschr Röntgenstr 2023; 195: 30 - 37.

Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis

PurposeThe aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers.Materials and MethodsRetrospective analysis including patients (ge 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0.ResultsIn total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases).ConclusionM-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

FOCUS phase 3 trial results: Percutaneous hepatic perfusion (PHP) with melphalan for patients with ocular melanoma liver metastases (PHP-OCM-301/301A).

9510 Background: Ocular melanoma, the most common intraocular malignancy, frequently metastasizes to the liver but to date there is no established standard of care for hepatic-dominant ocular melanoma patients. The FOCUS trial began as a randomized, Ph 3 trial (301) comparing PHP with best alternative care (BAC). The trial was subsequently amended (301A) to halt the BAC arm due to enrollment concerns. Methods: Eligible patients with hepatic-dominant ocular melanoma were randomized 1:1 to receive PHP or BAC (investigator’s choice of TACE, pembrolizumab, ipilimumab, or dacarbazine) on the 301 trial. All eligible patients received PHP on the 301A trial. PHP patients could receive up to 6 PHP treatments, repeated every 6-8 weeks with melphalan dosed at 3.0mg/kg ideal body weight (IBW). Patients with progressive disease (PD) were discontinued from study treatment and all patients are followed until death. Patientswere imaged every 12 (±2) weeks until PD. The primary endpoint, ORR (per RECIST 1.1) as assessed by Independent Review Committee, was characterized by the point estimate and 95% CI for each group (PHP and BAC). Results: 144 patients were enrolled overall; 102 were assigned to PHP (301: n = 43; 301A: n = 59) and 42 were assigned to BAC. 91 PHP patients received treatment (301: n = 40; 301A: n = 51) and 32 BAC patients received treatment. ORR among PHP patients was 35.2% (32/91; 95% CI: 25.44-45.88%). ORR among BAC patients was 12.5% (4/32; 95% CI: 3.51-28.99%; p= 0.0154). The median DOR was 14 months for PHP patients and not calculable for BAC patients. The DCR among PHP patients was 73.6% (67/91; 95% CI: 63.35-82.31%) and among BAC patients was 37.5% (12/32; 95% CI: 21.10-56.31%; p= 0.0002). The median PFS was 9.03 months (95% CI: 6.34-11.56) among PHP patients and was 3.12 months (95% CI: 2.89-5.65) among BAC patients ( p= 0.0007). The median OS was 20.53 months (95% CI: 16.59-24.35) among PHP patients and was 14.06 months (95% CI: 9.99-19.78) among BAC patients. With the last treatment occurring in May 2021, the OS, DOR, and PFS data continues to mature as patients are still being followed for survival. Among the 94 patients assessed for safety after treatment with PHP, 42.6% of patients experienced a serious treatment-emergent adverse event, the majority of which were hematological, transient in nature, and resolved without sequelae. There were no treatment related deaths in the trial. Conclusions: In this analysis of data from the FOCUS trial, PHP demonstrates superior ORR, DOR, DCR, PFS, and OS in comparison with BAC in the treatment of hepatic metastases from ocular melanoma. This therapy offers a potential option for patients with this rare indication that is associated with a poor prognosis and few treatment options. Clinical trial information: NCT02678572.

Safety and efficacy of combined melphalan percutaneous hepatic perfusion (M-PHP) and ipilimumab plus nivolumab (IPI+NIVO) in metastasized uveal melanoma (mUM): First results of the phase Ib part of the CHOPIN trial.

9560 Background: Uveal melanoma (UM) is the most frequent intraocular malignant tumor in adults. Approximately 50% of all patients (pts) will develop metastatic disease in the liver. Until now, there is no systemic therapy that has been shown to improve overall survival (OS), apart from tebentafusp. M-PHP is frequently applied for liver-only UM. However, the majority of pts eventually develops extrahepatic disease after M-PHP. IPI+NIVO has been shown to induce up to 20% response rates in mUM. Our observations that checkpoint inhibition was most effective on extrahepatic UM disease has led to the CHOPIN trial testing the combination of M-PHP and IPI+NIVO. Here we present the safety and efficacy data of the phase 1b part of CHOPIN. Methods: Adult pts with confirmed measurable hepatic mUM and WHO PS 0-1 were included. Two courses of 6 weekly M-PHPs (melphalan 3mg/kg, max 220mg) were combined with four courses IPI+NIVO three-weekly escalating the dosing from 1mg/kg each IPI+NIVO (cohort 1) to IPI 1mg/kg + NIVO 3mg/kg (cohort 2). Primary endpoint was safety of IPI+NIVO plus M-PHP. Secondary endpoints were best overall response (BOR) according to RECIST 1.1, progression-free survival (PFS), and OS. Results: 7 pts were included (4 male, median age 63.6 years (range 50-74)). Both cohorts were tolerated with no dose-limiting toxicities or deaths. Grade III/IV adverse events (AE) were observed in 2/3 pts in cohort 1 and in 3/4 pts in cohort 2 consisting of SIRS, febrile neutropenia, cholecystitis, neutropenia, thrombopenia, leukopenia, increased transaminases and fever. Grade I/II immune-related AEs occurred in all pts (myositis, hypothyroidism, hepatitis and dermatitis). BOR was 1 complete response, 5 partial responses and 1 stable disease accounting for an objective response rate (ORR) of 85.7%. At a median FU time of 20.2 months, 4 pts have an ongoing response. Currently the median PFS is 22.4 months, and all pts are still alive. Conclusions: Combining M-PHP with IPI+NIVO is safe at a dosing of IPI 1 mg/kg and NIVO 3 mg/kg and very promising ORR, PFS and OS have been observed. The randomized phase II part comparing M-PHP versus M-PHP+IPI+NIVO is currently recruiting. Clinical trial information: NCT04283890.

Temporal evolution in quality of life following melphalan percutaneous hepatic perfusion for patients with metastatic uveal melanoma.

e21520 Background: Recent studies have demonstrated a clear survival benefit of melphalan percutaneous hepatic perfusion (M-PHP) for liver metastases from ocular melanoma (mUM). Importantly, the survival benefit relating to each treatment cycle must be carefully balanced with changes in patient Quality of Life. We contribute our single centre findings on the temporal change in the quality of life after M-PHP therapy. Methods: We performed a retrospective analysis of the change in quality of life (QoL) using the Functional Assessment of Cancer Therapy - General (FACT-G) with mUM patients receiving M‐PHP at our institutions (n = 13). The FACT-G score which comprises physical (PWB), social (SWB), emotional (EWB) and functional (FWB) wellbeing were measured pre-procedure and at day 1, day of discharge, 7, 14 and 28 days after M-PHP therapy. Paired t-test was used to assess for any significant change in each QoL domain. Results: The baseline FACT-G score was 93.4 out of 108 +/- 14.7 (mean +/- std). Quality of life scoring significantly decreased immediately after the procedure (day 1; 84.8 +/- 13.1, p = 0.01) and gradually improved over time, with no significant difference in total score by the day of discharge; 88.7 +/- 13.7, c.f baseline p = 0.22). By day 28, there was a trend for overall improved QoL (96.6 +/-9.3, p = 0.25). Sub-score analysis revealed that by day 28 there was a statistically significant improvement in EWB (p = 0.02), a trend towards improved scores in PWB and SWB domains. FWB was slightly below baseline by day 28 (23.8 vs 23.2). Conclusions: Quality of life following M-PHP decreases immediately after therapy and is not significantly different from baseline by the day of discharge. By day 28 there is a trend towards improved overall quality of life. This study could provide the basis for determining the optimal time between treatment cycles.

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

BackgroundWhile immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease.MethodsOpen-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves.DiscussionThis is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver.Trial RegistrationThis trial was registered in the US National Library of Medicine with identifier NCT04283890. Registered as per February 2020 - Retrospectively registered.EudraCT registration number: 2018-004248-49.Local MREC registration number: NL60508.058.19.