New developments in the management of advanced melanoma &amp;ndash; role of pembrolizumab

Improta, Giuseppina; Leone, Isabella; Donia, Marco; Gieri, Stefania; Pelosi, Giuseppe; Fraggetta, Filippo

doi:10.2147/ott.s72823

Cited by 18 publications

(17 citation statements)

References 64 publications

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“…Pembrolizumab (MK-3475) is a highly selective humanized mAb of IgG4-kappa isotype, which directly blocks the interactions between PD-1 and the two ligands PD-L1 and PD-L2. 35 Pembrolizumab 2 mg/kg given q3w was granted accelerated approval in the United States for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 with disease progression during or after platinum-containing chemotherapy. Pembrolizumab is a potentially powerful and innovative strategy in cancer therapy.…”

Section: Anti-pd-1 Absmentioning

confidence: 99%

Highlights on immune checkpoint inhibitors in non–small cell lung cancer

Shen

Ren²

2017

Tumour Biol.

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The treatment of advanced or refractory non-small cell lung cancer has been historically difficult owing to the lack of studies on effective systemic cure. The progress in lung cancer treatment has plateaued, necessitating new options for additional benefits. Immune checkpoint proteins are co-inhibitory factors that can diminish the antigen-specific immune responses by attenuating the regulatory role of cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1, lymphocyte-activation gene 3, and T-cell immunoglobulin mucin-3. The therapeutic strategies targeting immune checkpoints mainly focus on the monoclonal antibody of these regulatory factors, which may facilitate clinical decision making. An enhanced understanding of the drug-resistance mechanisms and the therapeutic efficacy regulation will provide opportunities to improve the clinical outcomes of non-small cell lung cancer patients. Preclinical and clinical trials on these key immune-regulatory agents, which has heralded a new era in immuno-oncology in non-small cell lung cancer treatment, are currently in development. KeywordsNon-small cell lung cancer, immune checkpoint, cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1, programmed cell death ligand-1, tumor immunotherapy Date

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Section: Anti-pd-1 Absmentioning

confidence: 99%

Highlights on immune checkpoint inhibitors in non–small cell lung cancer

Shen

Ren²

2017

Tumour Biol.

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“…Therefore, there has been a shift to target other pathways, with alternative immunotherapies, for individuals such as our patient. Similar drugs (and targets) in melanoma that are being trialled include ipillimumab (CTLA-4 monoclonal antibody) and pembrolizumab or nivolmomab (PD-1 monoclonal antibodies) 7 9…”

Section: Discussionmentioning

confidence: 99%

“…PD-1 is an immune-inhibitory receptor expressed on cells of the immune system including B-lymphocytes and T-lymphocytes 9 18. PD-1 binds to either of its two ligands, PDL-1 or PDL-2.…”

Section: Discussionmentioning

confidence: 99%

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Limbic encephalitis following immunotherapy against metastatic malignant melanoma

Salam¹,

Lavin

Turan

2016

BMJ Case Reports

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Novel immunotherapies are increasingly being used to treat malignant melanoma. The use of such agents has been associated with triggering autoimmunity. However, there has been a paucity in reports of limbic encephalitis associated with these immunotherapies. Pembrolizumab, a monoclonal antibody against programmed cell death antigen (PD-1), is currently being trialled in the UK to treat malignant melanoma. We report a unique case of antibody-negative limbic encephalitis presenting 1 year after starting pembrolizumab, in the context of malignant melanoma. The patient presented with progressive cognitive decline. MRI of the brain revealed signal change within the limbic structures. Cerebrospinal fluid studies confirmed evidence of inflammation with raised white cell count and protein. We were able to prevent further progression of symptoms by stopping pembrolizumab and treating the patient instead with steroids. We advocate considering autoimmune neuroinflammation as a differential for neurological disorders presenting in patients receiving PD-1 antagonist treatment and immunotherapy in general.

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“…Mechanisms of acquired resistance include acquisition of additional mutations that restore MAP kinase signaling as well as activation of other signaling pathways such as PI3K/mTOR(5). With the continuing development of second line treatments including inhibitors of PI3K/mTOR and ERK(29) as well as immunotherapies(30), it is important to develop early detection methods of resistance to BRAF/MEK inhibitors to allow timely initiation of alternate therapies in order to maximize the chance of success.…”

Section: Discussionmentioning

confidence: 99%

Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood

Gee

Haq

Wargo

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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This study evaluates μNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients. In vitro assessment of melanocyte (MART-1, HMB45) and MAP kinase signaling (pERK, pS6K) molecule expression was performed in human cell lines, while clinical validation was performed in an IRB-approved study of melanoma patients undergoing biopsy and blood sampling. Tumor FNA and blood specimens were compared with BRAF genetic analysis and cross-sectional imaging. μNMR in vitro analysis showed increased expression of melanocyte markers in melanoma cells as well as increased expression of phosphorylated MAP kinase targets in BRAF-mutant melanoma cells. Melanoma patient FNA samples showed increased pERK and pS6K levels in BRAF mutant compared with BRAF WT melanomas, with μNMR blood circulating tumor cell level increased with higher metastatic burden visible on imaging. These results indicate μNMR technology provides minimally invasive point-of-care evaluation of tumor signaling and metastatic burden in melanoma patients.

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New developments in the management of advanced melanoma – role of pembrolizumab

Cited by 18 publications

References 64 publications

Highlights on immune checkpoint inhibitors in non–small cell lung cancer

Highlights on immune checkpoint inhibitors in non–small cell lung cancer

Limbic encephalitis following immunotherapy against metastatic malignant melanoma

Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood

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