Cutaneous adverse effects of the immune checkpoint inhibitors

Collins, Lindsey K.; Chapman, Michael; Carter, Joi B.; Samie, Faramarz H.

doi:10.1016/j.currproblcancer.2016.12.001

Cited by 170 publications

(132 citation statements)

References 22 publications

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“…These commonly include lichenoid reactions, eczema, and vitiligo. Other less frequent cutaneous adverse effects include actinic keratoses, squamous cell carcinoma, seborrheic keratoses, and psoriasis exacerbations . Furthermore, cutaneous adverse events occur more frequently when PD‐1 inhibitors are used in combination therapy with ipilimumab, an anti‐cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA4) .…”

Section: Discussionmentioning

confidence: 99%

“…Other less frequent cutaneous adverse effects include actinic keratoses, squamous cell carcinoma, seborrheic keratoses, and psoriasis exacerbations . Furthermore, cutaneous adverse events occur more frequently when PD‐1 inhibitors are used in combination therapy with ipilimumab, an anti‐cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA4) . There are few reports of adverse effects regarding combination use of nivolumab and cabiralizumab; however, recent ophthalmology literature describes a case of uveitis and scleritis in a patient receiving combination therapy …”

Section: Discussionmentioning

confidence: 99%

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Dermal elastolysis in the setting of combination immunotherapy

et al. 2019

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Multiple cutaneous side effects have been reported with the use of immunotherapies including programmed cell death protein 1 inhibitors. We report 2 patients who presented with papillary dermal elastolysis presenting as multiple, skin‐colored, wrinkled papules and atrophic macules following an inflammatory eruption in the setting of combination chemotherapy with nivolumab and cabiralizumab. These two cases highlight a novel finding, elastolysis in the setting of chemotherapy with nivolumab and cabiralizumab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dermal elastolysis in the setting of combination immunotherapy

et al. 2019

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“…For patients with opposing comorbidities or high tumor load and rapid progress, immunotherapy may not be suitable. Also, considerable percentages of patients suffer from intolerable adverse effects during immunotherapy, forcing them to quit therapy and alter the treatment strategy . Patients who receive BRAF/MEK inhibitors usually develop resistance within 9 to 12 months, despite a good initial tumor response .…”

Section: Introductionmentioning

confidence: 99%

The identification of patient‐specific mutations reveals dual pathway activation in most patients with melanoma and activated receptor tyrosine kinases in BRAF/NRAS wild‐type melanomas

Appenzeller

Gesierich

Thiem

et al. 2018

Cancer

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Background Increasing knowledge of cancer genomes has triggered the development of specific targeted inhibitors, thus providing a valuable therapeutic pool. Methods In this report, the authors analyze the presence of targetable alterations in 136 tumor samples from 92 patients with melanoma using a comprehensive approach based on targeted DNA sequencing and supported by RNA and protein analysis. Three topics of high clinical relevance are addressed: the identification of rare, activating alterations; the detection of patient‐specific, co‐occurring single nucleotide variants (SNVs) and copy number variations (CNVs) in parallel pathways; and the presence of cancer‐relevant germline mutations. Results The analysis of patient‐matched blood and tumor samples was done with a custom‐designed gene panel that was enriched for genes from clinically targetable pathways. To detect alterations with high therapeutic relevance for patients with unknown driver mutations, genes that are untypical for melanoma also were included. Among all patients, CNVs were identified in one‐third of samples and contained amplifications of druggable kinases, such as CDK4, ERBB2, and KIT. Considering SNVs and CNVs, 60% of patients with metastases exhibited co‐occurring activations of at least 2 pathways, thus providing a rationale for individualized combination therapies. Unexpectedly, 9% of patients carry potentially protumorigenic germline mutations frequently affecting receptor tyrosine kinases. Remarkably two‐thirds of BRAF/NRAS wild‐type melanomas harbor activating mutations or CNVs in receptor tyrosine kinases. Conclusions The results indicate that the integrated analysis of SNVs, CNVs, and germline mutations reveals new druggable targets for combination tumor therapy.

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“…The body's natural T‐cell immune response is overactivated and in turn attacks proliferating melanocytes to cause cell death to treat melanoma. The overactive T‐cell response is also the cause of the other cutaneous adverse events related to both of these medications . It has been described that heterozygous CTLA4 germline mutations can cause lymphocytic organ infiltration and thus, it is possible that drugs that affect this pathway can lead to lymphomas and pseudolymphomas as seen in our patient …”

Section: Discussionmentioning

confidence: 72%

Ipilimumab/nivolumab‐induced pseudolymphoma in a patient with malignant melanoma

et al. 2019

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Combination therapy with ipilimumab and nivolumab is an adjuvant treatment approach for metastatic melanoma that boasts increased 3‐year survival when compared with a single immunotherapy agent. Combination therapy, however, is associated with increased toxicities, especially cutaneous side‐effects. Here we present a patient with metastatic melanoma and a sudden eruption of painful nodules on the face and arms 10 days after the administration of the fourth dose of combination ipilimumab/nivolumab. Biopsies demonstrated lymphoid hyperplasia, not clinically or pathologically consistent with an infectious, malignant or autoimmune etiology; a diagnosis of pseudolymphoma secondary to ipilimumab/nivolumab was made. After a steroid taper, the lesions resolved, and the patient was restarted on nivolumab monotherapy 2 weeks later without recurrence of symptoms or disease.

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Cutaneous adverse effects of the immune checkpoint inhibitors

Cited by 170 publications

References 22 publications

Dermal elastolysis in the setting of combination immunotherapy

Dermal elastolysis in the setting of combination immunotherapy

The identification of patient‐specific mutations reveals dual pathway activation in most patients with melanoma and activated receptor tyrosine kinases in BRAF/NRAS wild‐type melanomas

Ipilimumab/nivolumab‐induced pseudolymphoma in a patient with malignant melanoma

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