Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations
Immune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to...
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2188719 |
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| author | Benjamin C. Park Sathya Narayanan Alexander Gavralidis Fei Ye Run Fan Ryan J. Sullivan Genevieve Boland Kerry L Reynolds Justin M. Balko Matteo S. Carlino Georgina V. Long Leyre Zubiri Alexander M. Menzies Douglas B. Johnson |
| author_facet | Benjamin C. Park Sathya Narayanan Alexander Gavralidis Fei Ye Run Fan Ryan J. Sullivan Genevieve Boland Kerry L Reynolds Justin M. Balko Matteo S. Carlino Georgina V. Long Leyre Zubiri Alexander M. Menzies Douglas B. Johnson |
| author_sort | Benjamin C. Park |
| collection | DOAJ |
| description | Immune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to difficulties in accurate diagnosis and management. Here, we conducted a multi-institution analysis of all patients with stage III/IV melanoma who developed RirAEs after being treated with ICIs (anti-PD-1/L1, anti-CTLA-4, and combination PD-1/CTLA-4 blockade) at three institutions (Vanderbilt University Medical Center, Massachusetts General Hospital, and Melanoma Institute of Australia). RirAEs were defined as those occurring in approximately <1% of patients treated with anti-PD-1 or <2% with combination. Of 2834 patients who received ICIs, 82 developed RirAEs and were more common with combination PD-1/CTLA-4 blockade (4.6%) vs. anti-PD-1/L1 agents (2.8%). Overall median time from ICI start to RirAE was 86 days (interquartile range 42–235 days) with significantly earlier onset in combination therapy (p < 0.001). The spectrum of RirAEs spanned across several organ systems. Most RirAEs were grade 2 (57 [41.3%]) and grade 3 (40 [29.0%]) with relatively few grade 4 (11 [8.0%]) or 5 (5 [3.6%]) events. Steroid re-escalation (21.4%) or additional immunosuppression (13.8%) were commonly required. RirAE recurrence occurred in 22.6% with ICI rechallenge; 37.1% had new irAEs with rechallenge. In conclusion, RirAEs associated with ICIs in melanoma patients occurred, in aggregate, in 2–5% of patients treated with anti-PD-1-based therapy. Steroid re-escalation and alternative immunosuppression use were frequently required but fatal irAEs were fairly uncommon. |
| format | Article |
| id | doaj-art-5fea4b8fffe544958754d98c4b9d90c4 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-5fea4b8fffe544958754d98c4b9d90c42024-12-27T17:34:39ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2188719Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentationsBenjamin C. Park0Sathya Narayanan1Alexander Gavralidis2Fei Ye3Run Fan4Ryan J. Sullivan5Genevieve Boland6Kerry L Reynolds7Justin M. Balko8Matteo S. Carlino9Georgina V. Long10Leyre Zubiri11Alexander M. Menzies12Douglas B. Johnson13School of Medicine, Vanderbilt University, Nashville, TN, USAMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USADepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USADepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USAMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USAMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USAImmune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to difficulties in accurate diagnosis and management. Here, we conducted a multi-institution analysis of all patients with stage III/IV melanoma who developed RirAEs after being treated with ICIs (anti-PD-1/L1, anti-CTLA-4, and combination PD-1/CTLA-4 blockade) at three institutions (Vanderbilt University Medical Center, Massachusetts General Hospital, and Melanoma Institute of Australia). RirAEs were defined as those occurring in approximately <1% of patients treated with anti-PD-1 or <2% with combination. Of 2834 patients who received ICIs, 82 developed RirAEs and were more common with combination PD-1/CTLA-4 blockade (4.6%) vs. anti-PD-1/L1 agents (2.8%). Overall median time from ICI start to RirAE was 86 days (interquartile range 42–235 days) with significantly earlier onset in combination therapy (p < 0.001). The spectrum of RirAEs spanned across several organ systems. Most RirAEs were grade 2 (57 [41.3%]) and grade 3 (40 [29.0%]) with relatively few grade 4 (11 [8.0%]) or 5 (5 [3.6%]) events. Steroid re-escalation (21.4%) or additional immunosuppression (13.8%) were commonly required. RirAE recurrence occurred in 22.6% with ICI rechallenge; 37.1% had new irAEs with rechallenge. In conclusion, RirAEs associated with ICIs in melanoma patients occurred, in aggregate, in 2–5% of patients treated with anti-PD-1-based therapy. Steroid re-escalation and alternative immunosuppression use were frequently required but fatal irAEs were fairly uncommon.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2188719Immune checkpoint inhibitor toxicityimmune checkpoint inhibitorsimmune related adverse eventsmelanomarare immune related adverse eventsuncommon immune related adverse events |
| spellingShingle | Benjamin C. Park Sathya Narayanan Alexander Gavralidis Fei Ye Run Fan Ryan J. Sullivan Genevieve Boland Kerry L Reynolds Justin M. Balko Matteo S. Carlino Georgina V. Long Leyre Zubiri Alexander M. Menzies Douglas B. Johnson Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations OncoImmunology Immune checkpoint inhibitor toxicity immune checkpoint inhibitors immune related adverse events melanoma rare immune related adverse events uncommon immune related adverse events |
| title | Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations |
| title_full | Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations |
| title_fullStr | Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations |
| title_full_unstemmed | Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations |
| title_short | Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations |
| title_sort | rare immune related adverse events in patients with melanoma incidence spectrum and clinical presentations |
| topic | Immune checkpoint inhibitor toxicity immune checkpoint inhibitors immune related adverse events melanoma rare immune related adverse events uncommon immune related adverse events |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2188719 |
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