Checkpoint inhibitors have improved outcomes in metastatic melanoma, with 4-year overall survival (OS) of 46% for anti-PD-1 alone or 53% in combination with anti-CTLA-4.
Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 with demonstrated durable response rate in metastatic melanoma.
High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors.
Novel immunotherapies including antibodies to programmed death ligand 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have become common therapies for neoplasms including metastatic melanoma and non-small cell lung cancer (NSCLC).
We established a prospective observational single-centre study and collected data from patients with either metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma, who were treated with anti-PD-1 (programmed cell death receptor 1), anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) or both CIs combined.
Immune checkpoint inhibitors revolutionized the treatment of several cancer types, including melanoma, and immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies is becoming a frontline therapy in metastatic melanoma.
Ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting.
Among immunotherapeutic approaches, antibodies targeting immune checkpoint inhibitors Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for treatment of metastatic melanoma and are in clinical trials for a variety of other cancers.
Another example is related to the administration of immune checkpoint inhibitors/ICIs (anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies), which are successfully used in metastatic melanoma.
Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others.
Immune checkpoint inhibitors including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies are yielding impressive responses in intracranial manifestations of metastatic melanoma and NSCLC.
However, it has not yet been clarified how TMB and ctDNA can be used to estimate response to combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma.
CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients.
We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer.
We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy.
An overlapping peptide library covering the full length of the XIAP protein was used to screen T cell responses of peripheral blood mononuclear cells (PBMC) from stage-IV melanoma patients treated with or without anti-CTLA4 (ipilimumab).
The relevance of GOT1 as a potential target in cancer therapy was supported by a lung adenocarcinoma RNA-seq data set as well as the GEO:GSE database of metastatic melanoma where GOT1 expression was increased.
The model estimated a cost associated with the management of grade ≥ 3 immune-related adverse events in patients with metastatic melanoma equal to €176.2 (95% CI 63.5-335.0) for anti-CTLA-4 therapy, €48.6 (95% CI 40.1-58.5) for the new anti-PDI therapies and €276.8 (95% CI 240.4-316.2) for the combined therapy.
Six French patients, three men and three women, mean age 66 years (range 44-74), all kidney transplant recipients, received ipilimumab (CTLA-4 inhibitor) for metastatic melanoma.
In this study, overall survival and response to anti-PD-1 (nivolumab, pembrolizumab) and anti-CTLA-4 (ipilimumab) therapy of 364 patients with metastatic melanoma were assessed comparing 236 NRAS-mutated patients with 128 NRAS wildtype patients.