Initial report of treatment of uveal melanoma with hepatic metastases with yttrium90 internal radiation followed by ipilimumab and nivolumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10025-10025 ◽  
Author(s):  
David R. Minor ◽  
Takami Sato ◽  
Marlana M. Orloff ◽  
Jason J. Luke ◽  
David J. Eschelman ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Checkpoint Inhibitors ◽  
Package Insert ◽  
Hepatic Metastases ◽  
Normal Liver ◽  
Hepatic Artery Infusion ◽  
Hepatic Toxicity ◽  
Internal Radiation ◽  
Initial Report ◽  
Grade 3

10025 Background: Hepatic metastases from uveal melanoma have no established therapy, with a median survival of only 6-12 months. To date therapy with checkpoint inhibitors has yielded minimal results. To take advantage of possible synergy between radiation and immunotherapy we treated patients with yttrium90 internal radiation followed by immunotherapy. Methods: Patients received yttrium90 (Sir-Spheres) via hepatic artery infusion in two treatments, one to each lobe 3-4 weeks apart, followed in 3-6 weeks by ipilimumab and nivolumab for 4 doses, then nivolumab maintenance. Results: We are presenting interim results because of the excessive toxicity seen when these FDA-approved modalities were used in sequence with the FDA-approved dosages. Initially dosing of yttrium90 (Y90) followed the package insert “BSA method” but after 8 patients we had 5 cases of grade 3-4 hepatic toxicity; in 4 cases the toxicity was observed after just the Y90. One case of cirrhosis occurred in a patient whose liver received 40-45Gy; her cirrhosis was felt most likely due to the Y90. Y90 dosing was then reduced to limit dosage to normal liver to 35Gy, and none of the next 5 patients have had more than grade 2 hepatic toxicity. Dosage to the normal liver is approximated by the MIRD formula: Actual delivered liver dose [Gy] = 50 * Administered activity [GBq] * (1 – Lung shunt fraction) / kg of treated liver. If calculated dose was > 35GY, dosage in GBq is reduced proportionally. Toxicity in the first 5 patients to receive immunotherapy included one grade 4, two grade 3 and two grade 2 hepatic toxicities, and only 3 of the 5 patients received more than one dose of ipilimumab. We then reduced dosing of ipilimumab from 3mg/kg x 4 to 1mg/kg x 4 because of this excessive autoimmune toxicity. Of 13 patients, 10 received both Y90 and immunotherapy, and 3 had responses (1 CR, 2 PR) with 3 patients stable > 5months. Median progression-free survival for all patients is 27 weeks and median overall survival is greater than 48 weeks. Treatment with Y90 produced an over 50% fall in peripheral blood lymphocytes which was reversed in most patients by the immunotherapy. Conclusions: With dose modifications this therapy appears feasible and objective tumor responses were seen. Sequential therapy with Y90 and immunotherapy appears tolerable if radiation to normal liver is limited to 35Gy and ipilimumab dose is 1mg/kg. Clinical trial information: NCT02913417.

Selective internal radiation therapy for hepatic metastases of uveal melanoma: a systematic review

2021 ◽  
Author(s):  
Harry Alexander ◽  
Daniel Wen ◽  
Michael Chu ◽  
Catherine Han ◽  
Peter Hadden ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Uveal Melanoma ◽  
Hepatic Metastases ◽  
Risk Of Bias ◽  
Low Grade ◽  
Selective Internal Radiation Therapy ◽  
Moderate Risk ◽  
Internal Radiation ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy

Objective: Uveal melanoma (UM) commonly metastasizes to the liver. Treatment usually consists of liver-directed therapies, such as selective internal radiation therapy (SIRT). This review aimed to assess the effectiveness and safety of SIRT for hepatic metastases from UM. Methods: The study protocol is available at OSF ( https://osf.io/vhyct/ ). EMBASE and MEDLINE were searched until July 2020, using terms related to SIRT and hepatic metastases from UM. Studies reporting outcomes of SIRT in patients with UM and at least one hepatic metastasis were included. Data on overall survival (OS), hepatic progression free survival (hPFS) or tumor response were collected. The Newcastle-Ottawa Scale (NOS) was used to assess risk of bias. Results: 11 studies were included, reporting outcomes for 268 patients with hepatic metastases from UM. Most studies (n = 9, 81.8%) were retrospective. Disease control was achieved in 170 patients (67.5%) and the median OS from time of SIRT was 12.3 months. Median hPFS was 5.4 months. Low-grade side-effects were common but serious complications were infrequent. There were two treatment-related deaths. The median NOS score was 6 (moderate risk of bias). Conclusion: SIRT appears to be a safe and effective treatment for patients with unresectable hepatic metastases from UM. The certainty of our results is unclear due to predominantly retrospective data with moderate risk of bias. Further prospective studies are required to explore the role of SIRT in UM. Advances in knowledge: SIRT appears to be a safe treatment for patients with unresectable hepatic metastases from UM. Further prospective work is required.

scholarly journals Long-Term Maintained Response to Selective Internal Radiation Therapy in an Oligometastatic Uveal Melanoma Patient Treated with Concomitant Anti-PD-1 Therapy

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 692
Author(s):  
Ilaria Proietti ◽  
Nevena Skroza ◽  
Luca Filippi ◽  
Nicoletta Bernardini ◽  
Alessandra Mambrin ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Uveal Melanoma ◽  
Hepatic Metastases ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Durable Response ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy ◽  
Primary Neoplasm

Uveal melanoma (UM) is a primary neoplasm of the eye arising from the melanocytes residing in the iris, ciliary body or choroid. It is the most frequent intraocular malignancy and often determines metastases at distant sites, with a peculiar tropism for the liver. Metastatic UM has a poor prognosis, as any treatment affects the natural course of this fatal disease. Herein, we report a case of a UM metastatic to the liver in a 54 year-old female patient, initially treated with nivolumab without success. The patient was then scheduled for selective internal radiation therapy (SIRT) while continuing immunotherapy. This combination led to a complete and durable response and the patient is currently free of disease, two years after the diagnosis of the hepatic metastases. The association between SIRT and immunotherapy (IT) has very promising perspectives for metastatic UM, especially considering the disappointing or contradictory results of classic chemotherapies, IT alone and targeted therapies. Furthermore, this combination has been shown to have a good security profile. However, further studies are needed to confirm the efficacy of associating SIRT and IT and to clarify some unsolved problems, such as the timing of administration of these two therapies.

90Y radioembolization for neuroendocrine cancers liver metastases provides sustained therapeutic effect with minimal toxicity.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 343-343
Author(s):  
Andrew S. Kennedy ◽  
Maha Elkordy ◽  
Elizabeth Estill Campbell ◽  
Brent Albertson ◽  
Scott Lee Sailer ◽  
...  
Keyword(s):  
Hepatic Metastases ◽  
Normal Liver ◽  
Clinical Problem ◽  
Left Lobe ◽  
Gastric Ulcers ◽  
Tumor Type ◽  
Treatment Volume ◽  
Grade 3 ◽  
Multiple Treatments ◽  
90Y Radioembolization

343 Background: Radioembolization (RE) is the delivery of radioactive microspheres (90Y) via the hepatic artery, which permanently implant preferentially in metastatic lesions, sparing adjacent normal liver. Metastatic neuroendocrine tumors in the liver are a common clinical problem which can be treated with RE. It is an outpatient procedure performed with increasing frequency worldwide for a variety of solid tumor types. Methods: A single institution retrospective review of all neuroendocrine patients treated with radioactive resin microspheres to control hepatic metastases. Details reviewed included: specifics of treatment and delivery, RECIST response at 3 and 6 months, acute and delayed radiation toxicities by CTC3ae, and analyses of tumor and radiation factors related to response and liver control. Results: A total of 56 patients; 26 male, 30 female, received a total of 85 separate treatments with resin 90Y microspheres. Treatment volume was all hepatic tumors with each treatment, usually selective whole liver in one fraction. Whole liver in 1 treatment comprised 86%, right lobe only in 10% and left lobe in 4%. Thirty-six patients (64.3%) received 1 treatment, 12 patients 2 fractions, 7 patients 3 fractions, and 1 patient 4 fractions. The median activity of 90Y delivered was 1.49 GBq (0.35 – 2.9 GBq). BSA approach was used for pretreatment activity calculations for all patients, with median of 100% planned activity delivered (26% - 147%). No grade 4 toxicities occurred, and only two grade 3 events were found (gastric ulcers). The median follow up is 24.2 mo. (1 – 93.4 mo.). RECIST at 3 and 6 months: CR 6.5%, SD 49.1%, PR 42.6% and PD 1.6%. Delivered activity (GBq) was associated with PR at 3 months (p=0.07, two-tailed t-test). Conclusions: Our experience is consistent with other published reports confirming the efficacy and low toxicity of this liver-directed ablative approach for unresectable neuroendocrine carcinomas. Multiple treatments to the whole liver were well tolerated. The BSA method of pretreatment radioactivity estimation is useful and safe in this tumor type.

scholarly journals Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 10 (8) ◽  
pp. 2618-2626
Author(s):  
Michael S. Sander ◽  
Igor Stukalin ◽  
Isabelle A. Vallerand ◽  
Siddhartha Goutam ◽  
Benjamin W. Ewanchuk ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Prognostic Index ◽  
Melanoma Patients

scholarly journals Immunological Backbone of Uveal Melanoma: Is There a Rationale for Immunotherapy?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1055 ◽  
Author(s):  
Ernesto Rossi ◽  
Giovanni Schinzari ◽  
Ilaria Grazia Zizzari ◽  
Brigida Anna Maiorano ◽  
Monica Maria Pagliara ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Clinical Benefit ◽  
Standard Treatment ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Phase Iii Clinical Trials

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease.

Early safety and efficacy from a phase I open-label clinical trial of CD137(4-1BB) agonistic antibody LVGN6051 as monotherapy and in combination with pembrolizumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2521-2521
Author(s):  
Siqing Fu ◽  
Wael A. Harb ◽  
Sapna Pradyuman Patel ◽  
Charles Lu ◽  
Daniel M. Halperin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antitumor Activity ◽  
Safety Profile ◽  
Single Agent ◽  
Human Study ◽  
Hepatic Metastases ◽  
Preliminary Evidence ◽  
Open Label ◽  
Grade 3 ◽  
Favorable Safety

2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of this study were to define the safety profile and to establish the recommended phase 2 dose (RP2D) of LVGN6051 alone or in combination with pembrolizumab. Pharmacokinetics, immunogenicity, pharmacodynamics and clinical efficacy will be also evaluated. Results: At the cut-off date on January 18, 2021, 16 subjects have been enrolled into the monotherapy cohorts (n=12, no DLT observed up to 7 mg/kg), and the combination cohort (n=4, ongoing at LVGN6051 2 mg/kg and pembrolizumab 200 mg, one DLT observed). No treatment-related adverse event (TRAE) was observed in monotherapy. Treatment-emergent adverse events (TEAE) in combination included increased ALT/AST, thrombocytopenia, and fatigue. In the combination cohort, one patient with predominant hepatic metastases and history of intermittent grade 2 hepatic impairment experienced grade 3 increased ALT/AST (DLT) on cycle 1 day 15 that were resolved to her baseline without corticosteroids on cycle 1 day 18. TRAE included increased ALT/AST, thrombocytopenia, neutropenia, nausea and fatigue. Seven of 10 evaluable patients in the monotherapy cohorts demonstrated stable disease with the longest treatment being 8+ months. Tumor reductions by >10% were observed in melanoma and neuroendocrine tumor on monotherapy. One patient with metastatic head and neck squamous cell carcinoma who had progressed on an anti-PD-L1 based therapy showed an immune partial response (iPR) for 6+ months to the combination therapy. Conclusions: Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed. While we continue assessing its safety profile, antitumor activity was observed in the LVGN6051 and pembrolizumab cohort. The favorable safety profile and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies. Clinical trial information: NCT04130542.

Sign in / Sign up

Export Citation Format

Share Document