Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management
Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospecti...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Skin Cancer |
| Online Access: | http://dx.doi.org/10.1155/2018/9602540 |
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| author | Anna J. Lomax Jennifer Lim Robert Cheng Arianne Sweeting Patricia Lowe Neil McGill Nicholas Shackel Elizabeth L. Chua Catriona McNeil |
| author_facet | Anna J. Lomax Jennifer Lim Robert Cheng Arianne Sweeting Patricia Lowe Neil McGill Nicholas Shackel Elizabeth L. Chua Catriona McNeil |
| author_sort | Anna J. Lomax |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab). IrAE occurred in 54%, most commonly dermatological (24%), rheumatological (22%), and thyroid dysfunction (12%). Thyroiditis was characterised by a brief asymptomatic hyperthyroid phase followed by a symptomatic hypothyroid phase requiring thyroxine replacement. Transplant rejection doses of methylprednisolone were necessary to manage refractory hepatotoxicity. A bullous pemphigoid-like skin reaction with refractory pruritus responded to corticosteroids and neuropathic analgesia. Disabling grade 3-4 oligoarthritis required sulfasalazine therapy in combination with steroids. The median interval between the last dose of anti-CTLA-4 antibody and the first dose of anti-PD-1 therapy was 2.0 months (range: 0.4 to 22.4). Toxicities may occur late; this requires vigilance and multidisciplinary management which may allow effective anticancer therapy to continue. Management algorithms for thyroiditis, hypophysitis, arthralgia/arthritis, colitis, steroid-refractory hepatitis, and skin toxicity are discussed. |
| format | Article |
| id | doaj-art-6a6c7629b3c04ae4a1a5ce60b738c779 |
| institution | Kabale University |
| issn | 2090-2905 2090-2913 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Skin Cancer |
| spelling | doaj-art-6a6c7629b3c04ae4a1a5ce60b738c7792025-02-03T01:23:59ZengWileyJournal of Skin Cancer2090-29052090-29132018-01-01201810.1155/2018/96025409602540Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical ManagementAnna J. Lomax0Jennifer Lim1Robert Cheng2Arianne Sweeting3Patricia Lowe4Neil McGill5Nicholas Shackel6Elizabeth L. Chua7Catriona McNeil8Chris O’Brien Lifehouse, Camperdown, NSW, AustraliaChris O’Brien Lifehouse, Camperdown, NSW, AustraliaConcord Repatriation General Hospital, Sydney, NSW, AustraliaSydney Medical School, University of Sydney, Camperdown, NSW, AustraliaSydney Medical School, University of Sydney, Camperdown, NSW, AustraliaSydney Medical School, University of Sydney, Camperdown, NSW, AustraliaCentenary Institute, Sydney, NSW, AustraliaSydney Medical School, University of Sydney, Camperdown, NSW, AustraliaChris O’Brien Lifehouse, Camperdown, NSW, AustraliaImmune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab). IrAE occurred in 54%, most commonly dermatological (24%), rheumatological (22%), and thyroid dysfunction (12%). Thyroiditis was characterised by a brief asymptomatic hyperthyroid phase followed by a symptomatic hypothyroid phase requiring thyroxine replacement. Transplant rejection doses of methylprednisolone were necessary to manage refractory hepatotoxicity. A bullous pemphigoid-like skin reaction with refractory pruritus responded to corticosteroids and neuropathic analgesia. Disabling grade 3-4 oligoarthritis required sulfasalazine therapy in combination with steroids. The median interval between the last dose of anti-CTLA-4 antibody and the first dose of anti-PD-1 therapy was 2.0 months (range: 0.4 to 22.4). Toxicities may occur late; this requires vigilance and multidisciplinary management which may allow effective anticancer therapy to continue. Management algorithms for thyroiditis, hypophysitis, arthralgia/arthritis, colitis, steroid-refractory hepatitis, and skin toxicity are discussed.http://dx.doi.org/10.1155/2018/9602540 |
| spellingShingle | Anna J. Lomax Jennifer Lim Robert Cheng Arianne Sweeting Patricia Lowe Neil McGill Nicholas Shackel Elizabeth L. Chua Catriona McNeil Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management Journal of Skin Cancer |
| title | Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management |
| title_full | Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management |
| title_fullStr | Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management |
| title_full_unstemmed | Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management |
| title_short | Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management |
| title_sort | immune toxicity with checkpoint inhibition for metastatic melanoma case series and clinical management |
| url | http://dx.doi.org/10.1155/2018/9602540 |
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