Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins - though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity.
Purpose
Some consider fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) clinically useful in patients presenting with nonspecific symptoms of malignancy, weight loss most commonly encountered. However, the appropriateness of such FDG-PET/CT studies remains to be clarified. This study evaluated the clinical value of FDG-PET/CT in patients referred primarily for weight loss.
Methods
From 2010 to 2017 in one academic center, 252 subjects underwent 254 FDG-PET/CT studies for weight loss as primary indication and retrospectively studied. Eighteen subjects were excluded due to ongoing active malignancy, weight loss not ultimately being the main indication for the FDG-PET/CT, technically inadequate FDG-PET/CT and insufficient follow-up. The FDG-PET/CT scans were considered clinically beneficial when true positive for the cause of weight loss that other investigations missed or would have missed, clinically neutral when true negative and clinically detrimental when false positive leading to additional investigations or false negative.
Results
Ultimately 234 unique subjects (236 FDG-PET/CT studies) were included. The average subject weight loss prior to the PET was 12 kg and average follow-up time post FDG-PET/CT scan was 3.4 years. The FDG-PET/CT scans were true positive in 24 studies (10%) with 8 studies (3%) clinically beneficial; false positive in 38 studies (16%) of which 26 led to 35 additional procedures and false negative in 13 studies (6%). In total, 39 (17%) FDG-PET/CT studies were clinically detrimental. The other 149 (63%) studies were true negative, clinically neutral.
Conclusion
FDG-PET/CT appears to have limited value in assessing subjects with weight loss as the leading clinical indication, proving to be five times more often detrimental than beneficial.
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