New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors

Ciccarese, Chiara; Alfieri, Salvatore; Santoni, Matteo; Santini, Daniele; Brunelli, Matteo; Bergamini, Cristiana; Licitra, Lisa; Montironi, Rodolfo; Tortora, Giampaolo; Massari, Francesco

doi:10.1517/17425255.2016.1120287

Cited by 49 publications

(59 citation statements)

References 59 publications

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“…Clinical trials of immune checkpoint blockade therapy with anti‐cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4) antibody (ipilimumab) or anti‐programmed cell death 1 (PD‐1) antibody (nivolumab or pembrolizumab) have resulted in durable antitumor responses in patients with melanoma as well as those with renal, lung and bladder cancers . The most commonly recognized side effects of these therapies are immune‐related adverse events (irAE) and most commonly involve the gastrointestinal tract, the liver and the skin . Dermatologic toxicity of any grade may be seen in up to 49–68% of patients undergoing ipilimumab treatment, and a meta‐analysis by Minkis et al reported an overall risk of 24%.…”

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confidence: 99%

“…Cutaneous irAEs show a broad range of clinical appearances in patients undergoing immune checkpoint blockade, including maculopapular, follicular, pruritic, pustular, vesicular, acneiform and exfoliative lesions . In a report of patients treated with anti‐PD‐1 antibody (either with nivolumab or pembrolizumab) Hwang et al reported that 49% developed dermatologic toxicity.…”

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Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

et al. 2016

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Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti-PD-1 and of 556 patients receiving anti-PD-L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti-PD-1/PD-L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient careKeywords: anti-CTLA-4, anti-PD-1, anti-PD-L1, dermatologic toxicities, immune checkpoint antibody Curry JL, Tetzlaff MT, Nagarajan P, Drucker C, Diab A, Hymes SR, Duvic M, Hwu W-J, Wargo JA, Torres-Cabala CA, Rapini RP, Prieto VG. Diverse types of dermatologic toxicities from immune checkpoint blockade therapy. J Cutan Pathol 2017; 44: 158-176.

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Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

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“…GI oncologists involved in clinical trials are facing a different adverse event scenario compared to the traditional chemotherapy one and need to improve their knowledge and skills to treat immune-related toxicities in a subset of patients who may already have baseline GI, liver function, and endocrine abnormalities from their underlying cancer or as complications from prior treatments. [113]. …”

Section: Future Perspectivesmentioning

confidence: 99%

Immunotherapy in Gastrointestinal Cancers

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et al. 2017

BioMed Research International

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Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials. In the present review a general overview is firstly provided followed by a focus on major findings on gastric, colorectal, and hepatocellular carcinomas. Finally, pathological and molecular perspectives are provided since many efforts are ongoing in order to identify possible predictive biomarkers and to improve patients' selection. Many issues are still unsolved in this field; however, we strongly believe that immunotherapy might positively affect the natural history of a subgroup of GI cancer patients improving outcome and the overall quality of life.

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“…However, restoration of the immune function with immune checkpoint antibody and management of therapy‐associated adverse reactions is challenging. Recognizing and treating the variety of adverse reactions that may occur with therapy will become more critical as more patients are offered these groundbreaking immunotherapies to enhance the antitumor immune response . Dermatologic toxicity is one of the common adverse events encountered with anti‐CTLA‐4 and anti‐PD‐1 antibody therapy and may be seen in up to 68 and 38% of patients, respectively .…”

Section: Introductionmentioning

confidence: 99%

Regressed melanocytic nevi secondary to pembrolizumab therapy: an emerging melanocytic dermatologic effect from immune checkpoint antibody blockade

et al. 2017

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New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors

Cited by 49 publications

References 59 publications

Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

Immunotherapy in Gastrointestinal Cancers

Regressed melanocytic nevi secondary to pembrolizumab therapy: an emerging melanocytic dermatologic effect from immune checkpoint antibody blockade

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