Hajir Ibraheim1,2, Samantha Baillie3, Mark A Samaan4, Hamzah Abu-Sbeih5, Yinghong Wang6, Nicholas J Talley7, Michael P Jones8, Nick Powell1,2. 1. Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK. 2. The Royal Marsden Hospital, London, UK. 3. Kings College Hospital, London, UK. 4. Department of Gastroenterology, Guy's and St Thomas' Hospital, London, UK. 5. University of Missouri-Kansas City, Kansas City, MO, USA. 6. The University of Texas MD Anderson Cancer Cente, Houston, TX, USA. 7. University of Newcastle, New Lambton, NSW, Australia. 8. Psychology Department, Macquarie University, North Ryde, NSW, Australia.
Abstract
BACKGROUND: Immune checkpoint inhibitors have revolutionised cancer treatment, but at the cost of off-target immune-mediated organ damage. This includes checkpoint inhibitor-induced enterocolitis which frequently requires hospitalisation and may be life-threatening. Empiric treatment typically includes corticosteroids and infliximab, although no large-scale studies have confirmed their effectiveness. AIM: To investigate the effectiveness of anti-inflammatory therapy in checkpoint inhibitor-induced enterocolitis METHODS: We performed a systematic review and meta-analysis of studies reporting clinical outcomes of checkpoint inhibitor-induced enterocolitis in adult cancer patients treated with anti-inflammatory agents. We searched Medline, EMBASE, and the Cochrane library through April and extracted the proportion of patients responding to anti-inflammatory therapy. Variation in effect size was studied using a random-effects meta-regression analysis, with checkpoint inhibitor agent and tumour type as the variables. RESULTS: Data were pooled from 1210 treated patients across 39 studies. Corticosteroids were effective in 59% (95% CI 54- 65) of patients, with response significantly more favourable in patients treated with anti-PD-1/L1 monotherapy, compared with anti-CTLA-4 containing regimens (78%, 95% CI 69-85 vs 56 %, 95% CI 49-63, P = 0.003), and more favourable in lung cancer patients compared with melanoma patients (88%, 95% CI 62-97 vs 55%, 95% CI 47-63, P = 0.04). Infliximab was effective in 81% (95% CI 73-87) of patients, and vedolizumab in 85% (95% CI 60-96). CONCLUSION: Corticosteroids, infliximab and vedolizumab, are effective in the treatment of checkpoint inhibitor-induced enterocolitis. Checkpoint inhibitor regimen and cancer type were significant moderators in response to corticosteroid therapy.
BACKGROUND: Immune checkpoint inhibitors have revolutionised cancer treatment, but at the cost of off-target immune-mediated organ damage. This includes checkpoint inhibitor-induced enterocolitis which frequently requires hospitalisation and may be life-threatening. Empiric treatment typically includes corticosteroids and infliximab, although no large-scale studies have confirmed their effectiveness. AIM: To investigate the effectiveness of anti-inflammatory therapy in checkpoint inhibitor-induced enterocolitis METHODS: We performed a systematic review and meta-analysis of studies reporting clinical outcomes of checkpoint inhibitor-induced enterocolitis in adult cancer patients treated with anti-inflammatory agents. We searched Medline, EMBASE, and the Cochrane library through April and extracted the proportion of patients responding to anti-inflammatory therapy. Variation in effect size was studied using a random-effects meta-regression analysis, with checkpoint inhibitor agent and tumour type as the variables. RESULTS: Data were pooled from 1210 treated patients across 39 studies. Corticosteroids were effective in 59% (95% CI 54- 65) of patients, with response significantly more favourable in patients treated with anti-PD-1/L1 monotherapy, compared with anti-CTLA-4 containing regimens (78%, 95% CI 69-85 vs 56 %, 95% CI 49-63, P = 0.003), and more favourable in lung cancer patients compared with melanoma patients (88%, 95% CI 62-97 vs 55%, 95% CI 47-63, P = 0.04). Infliximab was effective in 81% (95% CI 73-87) of patients, and vedolizumab in 85% (95% CI 60-96). CONCLUSION: Corticosteroids, infliximab and vedolizumab, are effective in the treatment of checkpoint inhibitor-induced enterocolitis. Checkpoint inhibitor regimen and cancer type were significant moderators in response to corticosteroid therapy.
Authors: James L Alexander; Hajir Ibraheim; Camellia Richards; Ben Shum; Polychronis Pavlidis; Nikki Hunter; Julian P Teare; Andrew Wotherspoon; Andrew Furness; Samra Turajlic; Lisa Pickering; James Larkin; Ally Speight; Sophie Papa; Nick Powell Journal: J Immunother Cancer Date: 2022-09 Impact factor: 12.469
Authors: James L Alexander; Hajir Ibraheim; Bhavisha Sheth; Jessica Little; Muhammad Saheb Khan; Camellia Richards; Nikki Hunter; Dharmisha Chauhan; Raguprakash Ratnakumaran; Kathleen McHugh; David J Pinato; Paul Nathan; Julia Choy; Shanthini M Crusz; Andrew Furness; Samra Turajlic; Lisa Pickering; James Larkin; Julian P Teare; Sophie Papa; Ally Speight; Anand Sharma; Nick Powell Journal: J Immunother Cancer Date: 2021-07 Impact factor: 13.751