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