Monique Krystyna van der Kooij shows that a combination of treatments enhancing the immune system can conquer metastasized melanoma in heavily pre-treated patients. Immunotherapy is not a new... Show moreMonique Krystyna van der Kooij shows that a combination of treatments enhancing the immune system can conquer metastasized melanoma in heavily pre-treated patients. Immunotherapy is not a new concept. However, in Leiden a milder, and therefore better tolerated preconditioning regimen is used before the immune cells are administered. This milder preconditioning, in combination with the patient’s own immune cells and an immune checkpoint inhibitor is unique. This thesis shows that this combination is safe and preliminary data also show that some patients have (lasting) clinical responses. A second important finding described in this thesis is that treatment with immune checkpoint inhibitors can safely be prescribed to patients with common autoimmune diseases. Approximately 1 in 10 metastatic melanoma patients suffer from such an autoimmune disease. Until now clinicians were hesitant to prescribe these immune checkpoint inhibitors out of fear of unleashing the autoimmune disease. Showing that this is not the case made it possible for this large group of patients to gain access to this often-successful treatment. However, immune checkpoint inhibitor monotherapy is not indicated for all patients with metastatic melanoma. Patients with uveal melanoma do not benefit from this type of treatment, and do suffer from the adverse events. Show less
Tong, T.M.L.; Kooij, M.K. van der; Speetjens, F.M.; Erkel, A.R. van; Meer, R.W. van der; Lutjeboer, J.; ... ; Kapiteijn, E. 2022
Background: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal... Show moreBackground: While 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.Methods: Open-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.Discussion: This 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. Show less
