Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab
Background Colitis is one of the common immune-related adverse events that leads to morbidity and treatment discontinuation of immunotherapy. The clinical presentation, endoscopic and histopathological features and best management of this toxicity are not well defined.Patients and methods Patients w...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001488.full |
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| author | Serigne Lo Georgina V Long Richard A Scolyer Matteo Carlino Kazi J Nahar Robert V Rawson Tasnia Ahmed Stephen Tattersall Neomal Sandanayake Christopher J Kiely Umaimainthan Palendira Alexander M Menzies |
| author_facet | Serigne Lo Georgina V Long Richard A Scolyer Matteo Carlino Kazi J Nahar Robert V Rawson Tasnia Ahmed Stephen Tattersall Neomal Sandanayake Christopher J Kiely Umaimainthan Palendira Alexander M Menzies |
| author_sort | Serigne Lo |
| collection | DOAJ |
| description | Background Colitis is one of the common immune-related adverse events that leads to morbidity and treatment discontinuation of immunotherapy. The clinical presentation, endoscopic and histopathological features and best management of this toxicity are not well defined.Patients and methods Patients with metastatic melanoma who received immunotherapy (programmed cell death protein 1 (PD1) antibodies, alone or in combination with a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (PD1 +CTLA-4)) and who developed clinically significant colitis (requiring systemic corticosteroids) were identified retrospectively from two academic centers. Clinical data were collected for all patients; endoscopic and histopathological data were examined in a subset.Results From May 2013 to May 2019, 118/1507 (7.8%) patients developed significant colitis; 80/553 (14.5%) after PD1+CTLA-4, 35/1000 (3.5%) PD1 alone, and three patients after Ipilimumab (IPI) alone. Combination therapy-induced colitis was more frequent (14.5% vs 3.5% in PD1 alone, p=<0.0001), had an earlier onset (6.3 weeks vs 25.7 weeks, p=<0.001), was more severe (grade 3/4 69% vs 31%, p=<0.001), and are more likely to require higher doses of steroids (91% vs 74%, p=0.01) than PD1 colitis. Among all patients treated with steroids (N=114), 54 (47%) responded and required no further therapy (steroid sensitive), 47 patients (41%) responded to infliximab (infliximab sensitive), and 13 (11%) were infliximab refractory and needed further immunosuppressive drugs. Infliximab-refractory patients all had onset within 4 weeks of immunotherapy commencement and were more likely to have an underlying autoimmune disease, have higher grade colitis, and require longer immunosuppression, yet had similar response and survival than other patients with colitis. Of 43 (37%) patients re-resumed treatment with PD1 monotherapy after colitis resolution, 16 (37%) of whom developed recurrent colitis. Endoscopic and histopathologic data were available for 64 patients. Most had left-sided colitis, with an increase in chronic inflammatory cells and neutrophils within the lamina propria, an increase in neutrophils in the surface epithelium, without increased lymphocytes or increased eosinophils. Infliximab-refractory colitis had a trend towards more confluent pancolitis with edema, erythema, ulceration, and absent vascularity with neutrophilic infiltration and erosion.Conclusion Clinically significant colitis varies in presentation, response to immunosuppression, and endoscopic/histologic features depending on the immunotherapy type. Infliximab-refractory colitis occurs early, is often high grade, and has adverse endoscopic and histopathologic features |
| format | Article |
| id | doaj-art-fa458e7182354c99bac3b7ae04a513ad |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-fa458e7182354c99bac3b7ae04a513ad2024-11-10T13:45:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001488Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumabSerigne Lo0Georgina V Long1Richard A Scolyer2Matteo Carlino3Kazi J Nahar4Robert V Rawson5Tasnia Ahmed6Stephen Tattersall7Neomal Sandanayake8Christopher J Kiely9Umaimainthan Palendira10Alexander M Menzies11Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia4 Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia5 Melanoma Institute Australia, Sydney, New South Wales, Australia4 Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia1 Melanoma Institute Australia, North Sydney, New South Wales, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia3 Gastroenterology, Royal North Shore Hospital, St Leonards, New South Wales, Australia3 Gastroenterology, Royal North Shore Hospital, St Leonards, New South Wales, Australia6 Department of Gastroenterology, Royal North Shore Hospital, St Leonards, New South Wales, Australia2 Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia7 Medical Oncology, Mater Hospital, Sydney, New South Wales, AustraliaBackground Colitis is one of the common immune-related adverse events that leads to morbidity and treatment discontinuation of immunotherapy. The clinical presentation, endoscopic and histopathological features and best management of this toxicity are not well defined.Patients and methods Patients with metastatic melanoma who received immunotherapy (programmed cell death protein 1 (PD1) antibodies, alone or in combination with a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (PD1 +CTLA-4)) and who developed clinically significant colitis (requiring systemic corticosteroids) were identified retrospectively from two academic centers. Clinical data were collected for all patients; endoscopic and histopathological data were examined in a subset.Results From May 2013 to May 2019, 118/1507 (7.8%) patients developed significant colitis; 80/553 (14.5%) after PD1+CTLA-4, 35/1000 (3.5%) PD1 alone, and three patients after Ipilimumab (IPI) alone. Combination therapy-induced colitis was more frequent (14.5% vs 3.5% in PD1 alone, p=<0.0001), had an earlier onset (6.3 weeks vs 25.7 weeks, p=<0.001), was more severe (grade 3/4 69% vs 31%, p=<0.001), and are more likely to require higher doses of steroids (91% vs 74%, p=0.01) than PD1 colitis. Among all patients treated with steroids (N=114), 54 (47%) responded and required no further therapy (steroid sensitive), 47 patients (41%) responded to infliximab (infliximab sensitive), and 13 (11%) were infliximab refractory and needed further immunosuppressive drugs. Infliximab-refractory patients all had onset within 4 weeks of immunotherapy commencement and were more likely to have an underlying autoimmune disease, have higher grade colitis, and require longer immunosuppression, yet had similar response and survival than other patients with colitis. Of 43 (37%) patients re-resumed treatment with PD1 monotherapy after colitis resolution, 16 (37%) of whom developed recurrent colitis. Endoscopic and histopathologic data were available for 64 patients. Most had left-sided colitis, with an increase in chronic inflammatory cells and neutrophils within the lamina propria, an increase in neutrophils in the surface epithelium, without increased lymphocytes or increased eosinophils. Infliximab-refractory colitis had a trend towards more confluent pancolitis with edema, erythema, ulceration, and absent vascularity with neutrophilic infiltration and erosion.Conclusion Clinically significant colitis varies in presentation, response to immunosuppression, and endoscopic/histologic features depending on the immunotherapy type. Infliximab-refractory colitis occurs early, is often high grade, and has adverse endoscopic and histopathologic featureshttps://jitc.bmj.com/content/8/2/e001488.full |
| spellingShingle | Serigne Lo Georgina V Long Richard A Scolyer Matteo Carlino Kazi J Nahar Robert V Rawson Tasnia Ahmed Stephen Tattersall Neomal Sandanayake Christopher J Kiely Umaimainthan Palendira Alexander M Menzies Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab Journal for ImmunoTherapy of Cancer |
| title | Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab |
| title_full | Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab |
| title_fullStr | Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab |
| title_full_unstemmed | Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab |
| title_short | Clinicopathological characteristics and management of colitis with anti-PD1 immunotherapy alone or in combination with ipilimumab |
| title_sort | clinicopathological characteristics and management of colitis with anti pd1 immunotherapy alone or in combination with ipilimumab |
| url | https://jitc.bmj.com/content/8/2/e001488.full |
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