Liver Metastases Are Associated with a Short Post-Progression Survival in a Real-World Group of Patients with Melanoma Treated with Checkpoint Inhibitors

Overview

Journal Oncol Ther

Specialty Oncology

Date 2024 Dec 11

PMID 39661321

Authors

Miriam Mengoni

Thomas Tuting

Evelyn Gaffal

Andreas D Braun

Affiliations

Soon will be listed here.

Abstract

Introduction: The introduction of immunotherapy (IT) has transformed clinical care of patients with metastatic melanoma. However, many patients still die as a result of progressive disease. Here we analyzed how IT improved survival in a real-world setting. Additionally, we investigated whether IT alters the dynamics and pattern of metastatic progression in different organs resulting from tissue-specific immune microenvironments.

Methods: We retrospectively compared a group of 61 patients with metastatic melanoma (24 female, 37 male) treated with IT between 2015 and 2018 with a historical control group of 56 patients with metastatic melanoma (21 female, 35 male) treated with chemotherapy between 2005 and 2008 regarding treatment response rates and overall survival as well as the timing and distribution of metastatic progression.

Results: Patients with metastatic melanoma treated with IT showed increased response rates and longer overall survival when compared with patients treated with chemotherapy. In addition, treatment with IT altered the dynamics but not the pattern of metastatic progression when compared with treatment with chemotherapy. Interestingly, patients receiving IT lived significantly longer after metastatic progression to lymph nodes, lungs and brain, but not after metastatic progression to the liver.

Conclusion: Our results confirm the efficacy of IT in a real-world setting. The altered dynamics of metastases supports studies suggesting a unique role of immune privilege in the liver tissue microenvironment that increases resistance to immunotherapy.

References

Louveau A, Harris T, Kipnis J . Revisiting the Mechanisms of CNS Immune Privilege. Trends Immunol. 2015; 36(10):569-577. PMC: 4593064. DOI: 10.1016/j.it.2015.08.006. View

Conway J, Rawson R, Lo S, Ahmed T, Vergara I, Gide T . Unveiling the tumor immune microenvironment of organ-specific melanoma metastatic sites. J Immunother Cancer. 2022; 10(9). PMC: 9472156. DOI: 10.1136/jitc-2022-004884. View

Luke J, Schwartz G . Chemotherapy in the management of advanced cutaneous malignant melanoma. Clin Dermatol. 2013; 31(3):290-7. PMC: 3709980. DOI: 10.1016/j.clindermatol.2012.08.016. View

Kirkwood J, Kottschade L, McWilliams R, Khushalani N, Jang S, Hallmeyer S . Real-world outcomes with immuno-oncology therapies in advanced melanoma: final results of the OPTIMIzE registry study. Immunotherapy. 2023; 16(1):29-42. DOI: 10.2217/imt-2022-0292. View

Jenkins R, Fisher D . Treatment of Advanced Melanoma in 2020 and Beyond. J Invest Dermatol. 2020; 141(1):23-31. PMC: 7541692. DOI: 10.1016/j.jid.2020.03.943. View

Tumeh P, Hellmann M, Hamid O, Tsai K, Loo K, Gubens M . Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC. Cancer Immunol Res. 2017; 5(5):417-424. PMC: 5749922. DOI: 10.1158/2326-6066.CIR-16-0325. View

Weiss S, Wolchok J, Sznol M . Immunotherapy of Melanoma: Facts and Hopes. Clin Cancer Res. 2019; 25(17):5191-5201. PMC: 6726509. DOI: 10.1158/1078-0432.CCR-18-1550. View

Zheng M, Tian Z . Liver-Mediated Adaptive Immune Tolerance. Front Immunol. 2019; 10:2525. PMC: 6856635. DOI: 10.3389/fimmu.2019.02525. View

Horn S, Stoltzfus K, Lehrer E, Dawson L, Tchelebi L, Gusani N . Epidemiology of liver metastases. Cancer Epidemiol. 2020; 67:101760. DOI: 10.1016/j.canep.2020.101760. View

10.

Yu J, Green M, Li S, Sun Y, Journey S, Choi J . Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med. 2021; 27(1):152-164. PMC: 8095049. DOI: 10.1038/s41591-020-1131-x. View

11.

Gershenwald J, Scolyer R, Hess K, Sondak V, Long G, Ross M . Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67(6):472-492. PMC: 5978683. DOI: 10.3322/caac.21409. View

12.

Tawbi H, Forsyth P, Hodi F, Algazi A, Hamid O, Lao C . Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol. 2021; 22(12):1692-1704. PMC: 9328029. DOI: 10.1016/S1470-2045(21)00545-3. View

13.

Wang X, Ji Q, Yan X, Lian B, Si L, Chi Z . The Impact of Liver Metastasis on Anti-PD-1 Monoclonal Antibody Monotherapy in Advanced Melanoma: Analysis of Five Clinical Studies. Front Oncol. 2020; 10:546604. PMC: 7552942. DOI: 10.3389/fonc.2020.546604. View

14.

Long G, Atkinson V, Lo S, Sandhu S, Guminski A, Brown M . Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018; 19(5):672-681. DOI: 10.1016/S1470-2045(18)30139-6. View

15.

Krenkel O, Tacke F . Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol. 2017; 17(5):306-321. DOI: 10.1038/nri.2017.11. View

16.

Cugurra A, Mamuladze T, Rustenhoven J, Dykstra T, Beroshvili G, Greenberg Z . Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science. 2021; 373(6553). PMC: 8863069. DOI: 10.1126/science.abf7844. View

17.

Serra-Bellver P, Versluis J, Oberoi H, Zhou C, Slattery T, Khan Y . Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study. Eur J Cancer. 2022; 176:121-132. DOI: 10.1016/j.ejca.2022.09.004. View

18.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

19.

Di Giacomo A, Chiarion-Sileni V, Del Vecchio M, Ferrucci P, Guida M, Quaglino P . Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021; 27(17):4737-4745. DOI: 10.1158/1078-0432.CCR-21-1046. View

20.

Pallares-Moratalla C, Bergers G . The ins and outs of microglial cells in brain health and disease. Front Immunol. 2024; 15:1305087. PMC: 11043497. DOI: 10.3389/fimmu.2024.1305087. View