1. Figure 5. Treatment of the checkpoint inhibitor related toxicity
Noha Abdel-Wahab1,2, Mohsin Shah1, and Maria E. Suarez-Almazor1
1Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, USA; and 2Rheumatology and Rehabilitation Department, Assiut University Hospitals, Egypt.
Use of Immune Checkpoint Inhibitors in the Treatment of Patients with Cancer and Preexisting Autoimmune Diseases: A Systematic Review of Case Reports
Title of the Poster Presentation Goes Here
Authors of the Poster Presentation Goes Here Institutional and/or Graduate School of Biomedical Sciences Affiliation Goes Here
More than 1/3 of patients with cancer and preexisting autoimmune disease treated with the checkpoint inhibitors do not develop toxicity
INTRODUCTION
RESULTS
Used checkpoint inhibitor therapy:
Ipilimumab: 82.4% (n=42)
Pembrolizumab: 7.8% (n=4)
Nivolumab: 7.8% (n=4)
Combined use of ipilimumab and nivolumab was reported in one patient
Figure 5. Treatment of the checkpoint inhibitor related toxicity
3,375 Excluded
3,705 Unique citations after duplicates removal
5,049 Citations (database + hand searches)
310 Excluded
20 Publications (51 case reports)
330 Potentially relevant citations
Checkpoint inhibitor therapy has dramatically increased the survival of patients with certain cancers such as melanoma and lung cancer.
Four checkpoint inhibitors have been approved by the US Food and Drug Administration for the treatment of cancer. These are targeted monoclonal antibodies against regulatory immune checkpoint molecules that inhibit T cell activation:
- Ipilimumab blocking CTLA4 (cytotoxic T lymphocyte antigen 4)
- Pembrolizumab and Nivolumab blocking PD-1 (programmed cell
death protein 1)
- Atezolizumab blocking PD-L1 (programmed cell death ligand protein 1)
However, their use can be limited by frequent immune related adverse events (irAEs) that can be fatal.
The exact mechanisms mediating the occurrence of irAEs are not completely understood.
Genetic background of the host could play a role since some individuals are more predisposed to autoimmunity than others.
In clinical practice, checkpoint inhibitors are often not recommended for patients with autoimmune disease, because of the concern of exacerbation of the underlying autoimmune condition, or susceptibility to severe irAEs.
Figure 1. Study selection flow chart
Status of the baseline autoimmune diseases at the start of the checkpoint inhibitor therapy:
Active with ongoing disease symptoms: 47.7% (n=21)
Non-active/stable disease: 52.3% (n=23)
Figure 3. Quality assessment
Exacerbation of baseline autoimmune diseases occurred with recurrent or exaggerated prior symptoms.
No difference was observed in the treatment related toxicity regardless of the presence or absence of an active autoimmune disease at the start of the checkpoint inhibitor therapy
Characteristics of the reported cases:
USA: 80.4% (n=41), Europe: 13.7% (n=7), and Japan: 5.9% (n=3)
Males: 67.0%. Median age: 55 (range 32-87) years
Metastatic melanoma: 92.2% (n=47), and lung cancer was reported in the remaining cases
Baseline autoimmune diseases are shown in Figure 2
Required to stop the checkpoint inhibitor therapy because of toxicity:
Stopped the treatment: 41.2% (n=7)
Continued the treatment: 58.8% (n=10)
Figure 2. Preexisting autoimmune diseases
Outcome of the checkpoint inhibitor related toxicity:
Improved: 93.3% (n=28)
Died from complications: 6.7% (n=2)
PURPOSE
Tumor response to the checkpoint inhibitor therapy:
Remission/partial response: 52.6% (n=10)
Stable disease: 10.5% (n=2)
Progressive disease: 36.8 (n = 7)
A systematic review of case reports can help identify new and unusual clinical findings and therapeutic adverse events.
We conducted such a review to summarize existing evidence in the literature on the use of checkpoint inhibitors in patients with cancer and preexisting autoimmune diseases.
Figure 4. Checkpoint inhibitor related toxicity in the included cases
CONCLUSION
Evidence from case reports shows that patients with cancer and preexisting autoimmune disease can benefit from the checkpoint inhibitor therapy, under careful supervision.
Additional studies are needed to establish the risk-benefit profile of the novel checkpoint inhibitor therapy in this population.
METHODS
We searched Medline, EMBASE, Web of Science, PubMed ePubs, and the Cochrane CENTRAL through June 2016 with no restrictions.
References of the included articles were also searched manually.
Study selection, data extraction, and quality appraisal was done independently by two investigators.
Quality appraisal of the included case reports was performed using guidelines for publishing adverse events reports (Kelly, 2007; pharmacoepidemiology and drug safety)
Acknowledgment
Prior treatment for autoimmune diseases:
Corticosteroids: 36.4% (n=16)
Synthetic DMARDs: 45.5% (n=20)
Biological DMARDs: 6.8% (n=3)
No prior treatment: 13.6% (n= 6)
Dr. Suarez-Almazor has a K24 career award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS grant AR053593).