The immune response may be related to cancer chemotherapy in several ways. First, the patient with advanced cancer may have depressed immunological responsiveness prior to commencement of chemotherapy. Secondly, chemotherapy itself may markedly influence the immune response. Finally, chemotherapy and immunotherapy may be used together in the treatment of specific neoplasms. Before discussing these in detail, it is pertinent to review the immune response and the techniques by which it can be assessed.

Immunological Aspects of Cancer Chemotherapy

Skin cancer and new treatment perspectives: a review.

Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms.

Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a ‘real world’ population of patients treated with ipilimumab to identify markers for treatment benefit. Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes. A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK. In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy.

Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma

Background
Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.

/pdf/immunological-and-biological-changes-during-ipilimumab-2dxintvl34.pdf

Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma

Background
Ipilimumab and vemurafenib have both been shown to improve survival in phase III trials of patients with metastatic melanoma. Although vemurafenib is associated with a rapid onset of activity, responses are often of limited duration. Conversely, responses to ipilimumab take time to develop, but can be durable. Currently, limited data exist on the sequencing of these agents in patients with the BRAFV600 mutation. The aim of this analysis was to identify factors that could potentially be used to optimise the order in which ipilimumab and BRAF inhibitors are administered in this patient population.

/pdf/sequencing-of-braf-inhibitors-and-ipilimumab-in-patients-8qxi5ljbn5.pdf

Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use

Based on the results of European Organization for Research and Treatment of Cancer (EORTC) 18991 trial, the US Food and Drug Administration (FDA) approved PEG-interferon α-2b (PEG-IFN) (Sylatron) as adjuvant therapy for high-risk melanoma. The EORTC 18991 trial was an open-label study of resectable stage III melanoma with 1,256 patients who were randomized to observation-alone or to treatment with PEG-IFN for up to 5 years. The median recurrence-free survival of the treatment groups was significantly longer, while overall survival, a secondary endpoint, was not significantly different between the two groups. This review, after a short summary of interferon α-2b trials, critically analyzes the EORTC18991 trial, as well as the subgroup results and future perspectives for this stage of disease.

Update on PEG-interferon α-2b as adjuvant therapy in melanoma.

8573 Background: Ipilimumab (Ipi) is approved in the US as first and second line therapy in patients with metastatic melanoma (MM) and in MM patients with previous therapy in the EU, based on an ov

Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival.

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Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use

Update on PEG-interferon α-2b as adjuvant therapy in melanoma.

Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival.