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PC05 - Immune Chekpoint Inhibitors in Real World - How Do We Treat NSCLC ''Special Populations'' (ID 87)
- Event: WCLC 2019
- Type: Pro-Con Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
PC05.03 - ICIs for Patients with Immune-Related Comorbidity (Now Available) (ID 3576)
14:30 - 16:00 | Presenting Author(s): Robert Pirker
Immune checkpoint inhibitors have recently been established as standard therapy for patients with advanced NSCLC. However, data on immune checkpoint inhibitors are limited for special patient populations such as elderly patients, patients with poor performance status and patients with immune-related comorbidity (1). Major clinical trials excluded patients with active autoimmune diseases requiring systemic steroids, patients with systemic immunosuppressive treatment, patients with interstitial lung disease or history of pneumonitis requiring systemic steroids, and patients with chronic viral infections (e.g. hepatitis, HIV). Patients with immune-related comorbidity include patients with autoimmune diseases, patients with organ transplants, patients with end-stage renal disease and patients with chronic viral infections. Data on the efficacy and safety of immune checkpoint inhibitors are limited for these patients and mainly based on patients with melanomas and only few patients with lung cancers.
Immune checkpoint inhibitors could result in unacceptable immune activation in patients with pre-existing autoimmune diseases (1). Based on a literature report, exacerbations of autoimmune symptoms occurred in about 1/3 of patients who had been treated with these drugs (1). Therefore, great caution with regard to the use of these drugs in patients with autoimmune diseases is mandated.
Patients with organ transplants have been excluded from clinical trials because of the concern of potential organ rejections. Nevertheless, few reports are available on immune checkpoint inhibitors in patients who had undergone prior organ transplantations (2-8). A recent overview (4) reported on 19 patients with the following characteristics: median age 59 (14-77) years, 74% males, melanoma (n=11), cutaneous squamous cell carcinoma (n=3), NSCLC (2) and hepatocellular ca (n=2), and duodenal cancer (n=1). Median time to start of checkpoint inhibitors after organ transplantation was 11 (range 1-25) years. Patients were treated with nivolumab (53%), ipilimumab (26%) or pembrolizumab (21%). Most patients received low dose prednisone. Graft rejections occurred in ten patients (7/12 kidney, 2/5 liver, and 1/2 heart transplants), particularly among patients who had been treated with anti PD-1 antibodies. Median time to rejection was 21 (range 5-60) days. Among nine patients without rejections, four had immune-related adverse events (hepatitis, colitis, pneumonitis, and dermatitis). A clinical benefit was seen in 57% of patients. This overview indicated that treatment with immune checkpoint inhibitors is associated with a high rate of transplant rejections. A high rejection rate was also reported by others (5). A retrospective analysis of patients with liver transplants indicated transplant rejections in two out of seven patients undergoing treatment with PD-1 inhibitors for hepatocellular carcinomas (n=5) and melanomas (n=2) (8). Taken together, patients with solid organ transplants have a clinically relevant risk of transplant rejection when treated with immune checkpoint inhibitors.
Little information is available for patients with impaired renal function including end-stage renal disease (1, 9). In a report on three patients undergoing hemodialysis, immune checkpoint inhibitors resulted in a partial response in one patient and in stable disease in two patients (9). The toxicity was acceptable except grade 2 pneumonitis in one patient. Based on a literature review, 10 out of 13 patients undergoing hemodialysis responded to immune checkpoint inhibitors. Grade 3-4 immune-related adverse events occurred in three patients. The authors concluded that immune checkpoint inhibitors may not be contra-indicated in patients undergoing hemodialysis but may result in significant toxicity (9).
Patients with chronic viral infections, especially hepatitis C, appear to have little risk of treatment-related increases in adverse events and, therefore, may be treated with immune chekpoint inhibitors under careful monitoring (1).
Although our knowledge on immune checkpoint inhibitors in patients with cancers is rapidly expanding, we still need more information on the efficacy and safety of these drugs in patients with immune-mediated diseases. Data in the real-world setting would be of particular interest. The gathering of these data could be facilitated by establishing registries on national and international levels. Until further information on the safety of these drugs will become available, immune checkpoint inhibitors should be administered with great caution and only after a careful risk benefit assessment in patients with immune-related comorbidity.
1. Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer 2017; 123: 1904-1911.
2. Kittai AS, Oldham H, Cetnar J, Taylor M. Immune checkpoint inhibitors in organ transplant patients. J Immunother 2017; 40: 277-281.
3. Chae YK, Galvez C, Anker JF, et al. Cancer immunotherapy in a neglected population: The current use and future of T-cell-mediated checkpoint inhibitors in organ transplant patients. Cancer Treat Rev 2018; 63: 116-121.
4. Hassan NA, Abudayyeh A, Shah M, et al. The outcome of checkpoint inhibitor therapy in patients with cancer and solid organ transplant: A systematic review of the literature. J Clin Oncol 2018; 36: 5 suppl, 41.
5. Abdel-Wahab N, Safa H, Abudayyeh A, et al. Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature. J ImmunoTher Cancer 2019; 7: 106.
6. Owonikoko TK, Kumar M, Yang S, et al. Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. Cancer Immunol Immunother 2017; 66: 45-50.
7. Charles J, Giovannini D, Terzi N, et al. Multi-organ failure induced by nivolumab in the context of allo-stem cell transplantation. Exp Hematol Oncol 2019; 8: 8.
8. DeLeon TT, Salomao MA, Aqel BA, et al. Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation: the Mayo Clinic experience. J Gastrointest Oncol 2018; 9: 1054-1062.
9. Cheun H, Kim M, Lee H, et al. Safety and efficacy of immune checkpoint inhibitors for end-stage renal disease patients undergoing dialysis: a retrospective case series and literature review. Invest New Drugs 2019; 37: 579-583.
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