- •Severe irAEs (grade III-IV) occurred earlier than mild irAEs (grade I-II) in this study.
- •The main medical needs in the management of immune-related adverse events (irAEs) involved the lung organ.
- •Rechallenge after previous irAE was assessed as feasible in 65% of cases.
- •Initiation of immunotherapy in patients with autoimmune comorbidity was assessed as feasible in 93% of cases.
- •A multidisciplinary approach could help to better appraise and manage irAEs in real life.
We investigated the activities of an ImmunoTOX board, an academic, multidisciplinary group of oncologists and organ specialists that adopts a real-life, case-by-case approach in the management of patients with immune-related adverse events (irAEs).
The ImmunoTOX assessment board was set up in 2016 at Gustave Roussy in France. It meets every 2 weeks to discuss the case-by-case management of patients presenting with irAEs. Here, we describe the ImmunoTOX board's activities between 2016 and 2019.
Over study period, 398 requests (concerning 356 patients) were submitted to the ImmunoTOX board. Most of the requests concerned the putative causal link between immunotherapy and the irAE (n = 148, 37%), followed by possible retreatment after temporary withdrawal because of an adverse event (n = 109, 27%), the clinical management of complex situations (n = 100, 25%) and the initiation of immunotherapy in patients with pre-existing comorbidities (n = 41, 10%). The ImmunoTOX board discerned 273 irAEs. The five organ systems most frequently involved by irAEs were lung (n = 58, 21%), gastrointestinal tract (n = 36, 13%), liver or biliary tract (n = 33, 12%), musculoskeletal system (n = 27, 10%), and nervous system (n = 23, 8%). The time to occurrence was shorter for severe irAEs (grade III and VI) than for mild irAEs (grades I and II), with medians of 47 and 91 days, respectively (p = 0.0216).
The main medical needs in the management of irAEs involved the lung organ. Severe irAEs were expected to occur earlier than mild irAEs. This real-life study can help to better estimate medical needs and therefore help to assess the management of irAEs.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to European Journal of Cancer
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- PD-Loma: a cancer entity with a shared sensitivity to the PD-1/PD-L1 pathway blockade.Br J Canc. 2019; 120: 3-5
- Immune-related adverse events associated with immune checkpoint blockade.N Engl J Med. 2018; 378: 158-168
- Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma.J Clin Oncol. 2017; 35: 785-792
- Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.Lancet. 2016; 387: 1837-1846
- Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol Off J Eur Soc Med Oncol. 2017; 28: iv119-iv142
- Immune-related adverse events with immune checkpoint blockade: a comprehensive review.Eur J Cancer Oxf Engl 1990. 2016; 54: 139-148
- Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline.J Clin Oncol. 2018 Jun 10; 36: 1714-1768
- Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis.JAMA Oncol. 2018; 4: 1721-1728
- Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper.Ann Oncol Off J Eur Soc Med Oncol ESMO. 2016; 27: 559-574
- A multidisciplinary toxicity team for cancer immunotherapy–related adverse events.J Natl Compr Canc Netw. 2019; 17: 712-720
- Immune-related adverse effects of cancer immunotherapy— implications for rheumatology.Rheum Dis Clin N Am. 2017; 43: 65-78
- Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the society for immunotherapy of cancer (SITC) toxicity management working group.J Immunother Canc. 2017; 5: 95
- Good pharmacovigilance practices for the americas.2011 ([published online June])
- HHS. International conference on harmonisation; guidance on addendum to E2C clinical safety data management: periodic safety update reports for marketed drugs; availability. Notice.Fed Regist. 2004; 69: 5551-5552
- Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma.Ann Oncol Off J Eur Soc Med Oncol. 2018; 29: 250-255
- Safety and efficacy of Re-treating with immunotherapy after immune-related adverse events in patients with NSCLC.Cancer Immunol Res. 2018; 6: 1093-1099
- Evaluation of readministration of immune checkpoint inhibitors after immune-related adverse events in patients with cancer.JAMA Oncol. 2019; (published online June 6)https://doi.org/10.1001/jamaoncol.2019.1022
- Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease.Eur J Cancer Oxf Engl 1990. 2018; 91: 21-29
- Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab.Ann Oncol Off J Eur Soc Med Oncol. 2017; 28: 368-376
- Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer.Cancer Immunol Immunother CII. 2019; 68: 917-926
- Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review.Ann Intern Med. 2018; 168: 121-130
- Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports.PloS One. 2016; 11e0160221
- Multidisciplinary cancer clinics: their time has come.J Surg Oncol. 1998; 69: 203-205
- Multidisciplinary care in oncology: medicolegal implications of group decisions.Lancet Oncol. 2006; 7: 951-954
- The impact of multidisciplinary team meetings on patient assessment, management and outcomes in oncology settings: a systematic review of the literature.Canc Treat Rev. 2016; 42: 56-72
- Efficacy of the multidisciplinary tumor board conference in gynecologic oncology: a prospective study.Medicine (Baltim). 2017; 96e8089
- Impact of a multidisciplinary tumour board meeting for upper-GI malignancies on clinical decision making: a prospective cohort study.Int J Clin Oncol. 2013; 18: 214-219
- A multidisciplinary approach to the management of urologic malignancies: does it influence diagnostic and treatment decisions?.Urol Oncol Semin Orig Invest. 2011; 29: 378-382
- Colon immune-related adverse events: anti-CTLA-4 and anti-PD-1 blockade induce distinct immunopathological entities.J Crohns Colitis. 2017; 11: 1238-1246
- Ipilimumab-induced toxicities and the gastroenterologist: ipilimumab-induced toxicities.J Gastroenterol Hepatol. 2015; 30: 657-666
- Beyond maximum grade: modernising the assessment and reporting of adverse events in haematological malignancies.Lancet Haematol. 2018; 5: e563-e598
- Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center.J Clin Oncol. 2015; 33: 3193-3198
- New therapeutic perspectives to manage refractory immune checkpoint-related toxicities.Lancet Oncol. 2019; 20: e54-e64
Published online: March 12, 2020
Accepted: February 11, 2020
Received: February 6, 2020
© 2020 Elsevier Ltd. All rights reserved.