18F-FDG PET/CT versus conventional investigations for cancer screening in autoimmune inflammatory myopathy in the era of novel myopathy classifications.

BACKGROUND: To compare the performance of fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) and conventional tests for cancer screening in autoimmune inflammatory myopathy (AIM) patients. PATIENTS AND METHODS: We carried out a retrospective cohort study of AIM patients from one academic center in Montreal, Canada, classified using myositis-specific antibodies, who underwent F-FDG PET/CT between April 2005 and February 2018 and were followed up on average 3.5±2.4 years. Patients were excluded if follow-up was insufficient, AIM diagnosis was indeterminate, and/or malignancy was diagnosed before an F-FDG PET/CT scan. Demographic/clinical data, F-FDG PET/CT results, and available conventional screening tests results were retrieved from electronic and paper medical records. RESULTS: 100 F-FDG PET/CT studies in 63 unique patients [31/63 dermatomyositis (DM), 25/63 overlap myositis, 1/63 inclusion body myositis, 1/63 polymyositis, 1/63 orbital myositis and 4/63 unspecified myositis] were evaluated. Three patients, all classified as DM, were diagnosed with cancer during follow-up with conventional cancer screening tests: breast cancer detected by mammography; squamous cell carcinoma of the skin detected by physical examination; and multiple myeloma detected by blood work. F-FDG PET/CT did not detect any malignancy and led to more additional biopsies than conventional screening (8 vs. 5). CONCLUSION: F-FDG PET/CT does not appear to be useful in cancer screening for AIM patients compared with conventional screening and carries potential harms associated with follow-up investigations. The risk of cancer in AIM differs by myositis-specific antibodies-defined subsets and cancer screening is likely to be indicated only in high-risk patients, particularly DM. These results, replicated in larger, multicentered studies, may carry significant consequences for optimal management of AIM and health resource utilization.

A case of severe Pembrolizumab-induced neutropenia.

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.