Immunotherapy in melanoma: Recent advances and future directions

Franklin, Cindy; Livingstone, Elisabeth; Roesch, Alexander; Schilling, Bastian; Schadendorf, Dirk

doi:10.1016/j.ejso.2016.07.145

Cited by 219 publications

(153 citation statements)

References 34 publications

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“…For oligometastatic disease, surgery with or without adjuvant systemic therapy can still be the treatment of choice (Lasithiotakis and Zoras, 2017); for locoregional unresectable disease (stage IIIC), surgery can be performed after downstaging with (combination) immunotherapy or BRAF and/or MEK inhibitors. For most patients with unresectable stage IIIC or IV disease, systemic therapy is the first line of treatment (Amann et al, 2017;Franklin et al, 2017).…”

Section: Surgerymentioning

confidence: 99%

ECCO essential requirements for quality cancer care for melanoma: Defining how to organise care

Wouters

2018

European Journal of Surgical Oncology

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Section: Surgerymentioning

confidence: 99%

ECCO essential requirements for quality cancer care for melanoma: Defining how to organise care

Wouters

2018

European Journal of Surgical Oncology

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“…The tremendous discovery of the efficacy of immunotherapy in melanoma paved the way for its application in other types of cancers such as non-small cell lung cancer, head and neck cancers, renal cell carcinoma, and urothelial carcinoma of the bladder. 1 The US Food and Drug Administration approved 3 different immunotherapeutic drugs for the treatment of advanced melanoma: ipilimumab, which is a monoclonal antibody against the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and nivolumab and pembrolizumab, which are monoclonal antibodies against the programmed cell death-1 (PD-1) receptor. 2,3 These monoclonal antibodies are also referred to as "immune checkpoint inhibitors" because they remove the brakes (the checkpoints) from the immune system and activate T cells.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 These monoclonal antibodies are also referred to as "immune checkpoint inhibitors" because they remove the brakes (the checkpoints) from the immune system and activate T cells. [1][2][3] With activation of the T cells to fight cancer, there is always a chance that these activated T cells might attack normal tissues, leading to immune-related adverse events such as colitis, hepatitis, pneumonitis, endocrinopathies, skin rash, and rarely encephalitis. [1][2][3] Immune-mediated hematologic toxicity could vary from anemia, thrombocytopenia, and leukopenia to rarely pancytopenia (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] With activation of the T cells to fight cancer, there is always a chance that these activated T cells might attack normal tissues, leading to immune-related adverse events such as colitis, hepatitis, pneumonitis, endocrinopathies, skin rash, and rarely encephalitis. [1][2][3] Immune-mediated hematologic toxicity could vary from anemia, thrombocytopenia, and leukopenia to rarely pancytopenia (Table 1). [4][5][6][7][8][9][10][11][12][13][14] We present the first case, to our knowledge, of pembrolizumab-induced pancytopenia to be reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Pembrolizumab-Induced Pancytopenia: A Case Report

Atwal

Joshi

Ravilla

et al. 2017

TPJ

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Introduction: Programmed death receptor-1 blockade with pembrolizumab is approved by the US Food and Drug Administration to treat patients with metastatic melanoma. Activating T cells to fight cancer may cause immune-mediated adverse events. Pembrolizumab-induced pancytopenia has not been previously reported in the medical literature, to our knowledge.Case Presentation: A 52-year-old Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced multiple adverse events along her course of therapy with pembrolizumab, ranging from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia after the 18th cycle of pembrolizumab. Severe pancytopenia improved after high-dose corticosteroids and a 5-day course of intravenous immunoglobulin therapy.Discussion: In our case, pembrolizumab-induced Grade 4 pancytopenia resolved via a combination of corticosteroids and intravenous immunoglobulins. Pancytopenia reached a nadir in 10 weeks, and it took 16 weeks for meaningful recovery.

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“…Ipilimumab, a monoclonal antibody that targets CTLA-4, has been granted approval for use in the advanced unresectable disease. Nivolumab and pembrolizumab, which target the PD-1 inhibitors and thereby prolonging overall survival in patients with advanced or metastatic melanoma and also in relapsed or refractory cases, have been provided accelerated approval by competent authorities [9][10][11] . The combination of ipilimumab and nivolumab provides higher response rates, greater tumor control, and longer progression-free survival as compared to monotherapy with either of these agents.…”

mentioning

confidence: 99%

Shifting paradigms in the management of metastatic and unresectable melanoma

Suhag

Vats

2017

Adv Mod Oncol Res

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[1,2] . More than 80% of cases occur in developed countries and melanoma forms the sixth most common cancer in the developed world. The incidence of melanoma has witnessed an upward trend in the last five decades and the number of new cases diagnosed annually is increasing faster than for any other cancer in most of the developed countries [3] . The mainstay of management of melanoma is essentially early detection and surgical excision, and five-year survival rates of >90% and 80% for stage I and II lesions, respectively, have been reported. The chances for cure for locoregionally advanced and metastatic disease decrease drastically, with a survival of 50% for Stage III patients while Stage IV patients historically had a median survival of about 8-9 months and a three-year overall survival rate of about less than 15% [4,5] . Systemic treatment with a definitive survival benefit appeared to be a remote possibility traditionally. There has been recently established data which indicates an encouraging therapeutic response for metastatic melanoma with the evolution of several heterogeneous novel agents, and there is a hope for better overall survival for such patients, most of whom were deemed unfit for any curative systemic therapy until recently [6] .Traditionally, the systemic treatment for metastatic melanoma was characterized by low response rates and significant toxicities. One such agent was dacarbazine, which used to yield a response rate of about 20% and median response of a duration of about six months without any benefit in overall survival. Another such agent was high-dose interleukin (IL)-2, which provided about 6%-16% response rate and a progression-free survival of about 13 months. Interferon (IFN)-α was approved as the first agent in the adjuvant setting for selected high-risk resected cases and resulted in significant improvement in diseasefree survival (DFS) and in some prospective randomized trials, with a benefit on overall survival in some studies; however, its use was associated with significant toxicity. Temozolomide is an oral alkylator with a cytotoxic effect identical to dacarbazine. Unlike the later drug, temozolomide is administered easily through oral route and it crosses the blood-brain barrier, thus exhibiting cytotoxic effect on brain metastases. Combination chemotherapy has also been tested in several studies, without showing any improvement in response rates [7,8] .Immunotherapy for advanced and metastatic melanoma has been extensively evaluated in the recent years, and Suhag V and Vats P

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Immunotherapy in melanoma: Recent advances and future directions

Cited by 219 publications

References 34 publications

ECCO essential requirements for quality cancer care for melanoma: Defining how to organise care

ECCO essential requirements for quality cancer care for melanoma: Defining how to organise care

Pembrolizumab-Induced Pancytopenia: A Case Report

Shifting paradigms in the management of metastatic and unresectable melanoma

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