Ipilimumab (Anti-Ctla-4 Mab) in the treatment of metastatic melanoma: Effectiveness and toxicity management

Abstract

In the last years the onset of new therapies changed the management of malignant melanoma. Anti CTLA-4 antibody ipilimumab was the first drug to achieve a significant improvement in survival of advanced stage melanoma. This new therapeutic agent is characterized by a number of side effects that are totally different from those of traditional chemotherapy, mainly caused by the immune system activation. The purpose of this paper is to underline the central role of ipilimumab in the treatment of metastatic melanoma and to characterize related adverse events in terms of incidence, duration and severity of presentation. The early recognition of these side effects is crucial in order to ensure an appropriate management of the toxicities, thus reducing the long term clinical sequelae and the inappropriate treatment discontinuation.

Ipilimumab and Its Derived EGFR Aptamer-Based Conjugate Induce Efficient NK Cell Activation against Cancer Cells

“…Recent reports [17] have evidenced the unexpected expression of CTLA-4 on tumor cells, thus, we investigated the effects of the human anti-CTLA-4 mAb ipilimumab [22] on a panel of cell lines expressing different levels of this antigen to verify whether it has also a direct anti-tumor cell activity independent from the immune response. To this aim, we firstly examined the expression of CTLA-4 on the surface of different cell lines by cell enzyme-linked immunosorbent assays (ELISA) ( Figure 1A).…”

“…Ipilimumab was approved by the U.S. FDA in 2011 for the treatment of metastatic melanoma [2,19], and several clinical trials have been started for other solid tumors, such as non-small-cell lung cancer (NSCLC), and renal cell and prostate carcinomas [20]. Nevertheless, the monotherapy approach seemed to be not effective in the case of poor immunogenic tumors, thus inducing studies and trials focused on the combination of ipilimumab with other anti-tumor drugs, such as IL-2, peptide vaccine, chemotherapy drug decarbazine [21][22][23], or with other immune checkpoint inhibitors. Among them, the anti-PD-1 mAb nivolumab, in combination with ipilimumab, has shown two-year overall survival (OS) rates of 40% in patients affected by NSCLC [24].…”

From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review

“…The five-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with anti-CTLA-4 + dacarbazine vs. 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine ( p = 0.002, CA184-024, NCT00324155) [ 59 ]. Toxicity associated with ipilimumab includes immune-related symptoms such as dermatitis, colitis, diarrhea and, less commonly, hepatitis, uveitis and hypophysitis [ 60 ]. Pembrolizumab and nivolumab (anti-PD1): After the ipilimumab proof of concept that a checkpoint blockade could actually be an effective strategy to treat melanoma, pembrolizumab and nivolumab were investigated for the same indication, even if (or maybe especially because) they are selective for another receptor which is usually expressed on immune T cell surface—PD-1.…”

“…The five-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with anti-CTLA-4 + dacarbazine vs. 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine ( p = 0.002, CA184-024, NCT00324155) [ 59 ]. Toxicity associated with ipilimumab includes immune-related symptoms such as dermatitis, colitis, diarrhea and, less commonly, hepatitis, uveitis and hypophysitis [ 60 ].…”

Autoimmun endocrinopathiák kapcsolata a diabetes mellitussal

“…23 Az aldesleukinhez hasonló indikációs körben alkalmazott CTLA-4-gátló ipilimumab adása mellett a betegek több mint felénél jelentkezett valamely endokrin diszfunkció vagy nem endokrin autoimmun kórkép. 24 A hematológiai indikációk mellett napjainkban a sclerosis multiplex kezelésében is bevezetett CD52-gátló alemtuzumab, különösen nagyobb dózisok használata mellett, 30%-ban okoz autoimmun pajzsmirigybetegséget, amely akár 2 évvel a kezelés befejezése után is manifesztálódhat. 25 A HIV-kezelésben alkalmazott nagy hatékonyságú antiretrovirális kezelés (highly active antiretroviral therapy -HAART) kombinációk mellett ritkán Basedow-kór, még ritkábban egyéb endokrin betegségek megjelenését írták le.…”