BackgroundAntibodies against programmed death 1 (PD-1) receptor and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have transformed the systemic treatment of melanoma and many other cancers. Understanding the spectrum of benign findings and atypical response patterns seen in immune checkpoint blockade is important for accurately assessing treatment response as these immunotherapies become more widely used.Case presentationWe report a 63-year-old man with metastatic melanoma successfully treated with combination CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), after non-response to pembrolizumab monotherapy. The initial impression of disease progression, based on cutaneous and PET/CT findings of increased fluoro-2-deoxy-D-glucose (FDG) uptake in benign lymphoid tissue, proved to be erroneous after assiduous review of radiographic imaging and correlative pathology.ConclusionsThese findings indicate that increased FDG uptake in benign lymphoid tissue seen on PET/CT may be a surrogate marker of immune activation and treatment response. Prospective studies will be invaluable in validating immune-related radiographic findings as a prognostic biomarker of response in cancer patients being treated with immune checkpoint blockade.
CD70 is a member of the tumor necrosis factor (TNF) receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T cell lymphomas; and conducted pre-clinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate, using patient-derived cutaneous T cell lymphoma (CTCL PDX) models. CD70 expression was examined by immunohistochemical stains in 46 diagnostic specimens of T cell lymphomas. The activities of SGN-CD70A in growth inhibition and apoptosis induction were examined in CTCL cell lines and primary CTCL tumor cells. Using previously established CTCL PDXs, we conducted a dose-finding trial, followed by a phase II-like trial, to evaluate the optimal dosing and the efficacy of SGN-CD70A in tumor-bearing PDX animals. The therapeutic efficacy of SGN-CD70A was measured by tumor-associated cell-free DNA (cfDNA) and survival of treated PDXs. We found that CD70 is highly expressed in T cell lymphomas, especially in CTCL. SGN-CD70A inhibited cell growth and induced apoptosis in CD70-expressing CTCL cell-lines and primary tumors cells. Additionally, SGN-CD70A at 100 µg/kg and 300 µg/kg prolonged survival of PDXs in a dose-dependent manner. Finally, treatment with three doses of SGN-CD70A at 300 µg/kg was superior to single dose treatment in survival prolongation (median survival: 111 days vs. 39 days, p=0.017). Most importantly, multiple-dosing of SGN-CD70A induced complete eradication of established tumors in PDXs measured by cfDNA. Our results demonstrated marked anti-tumor activity of SGN-CD70A in CTCL PDXs, providing compelling support for its clinical investigation.
The diagnosis of NUSI is important to consider in patients who are seen with antihistamine-resistant urticaria in combination with systemic inflammatory symptoms. Interleukin 1 blockade is a viable option for therapy.
Sweet's syndrome is an acute febrile neutrophilic dermatosis which usually presents as an idiopathic disorder but can also be drug induced, associated with hematopoetic malignancies and myelodysplastic disorders, and more, infrequently, observed in autoimmune disorders. Sweet's syndrome has been reported in three cases of neonatal lupus, three cases of hydralazine-induced lupus in adults, and in nine pediatric and adult systemic lupus erythematosus (SLE) patients. We describe three additional adult cases of Sweet's associated with SLE and provide a focused review on nondrug-induced, nonneonatal SLE and Sweet's. In two of three new cases, as in the majority of prior cases, the skin rash of Sweet's paralleled underlying SLE disease activity. The pathogenesis of Sweet's remains elusive, but evidence suggests that cytokine dysregulation may be central to the clinical and pathological changes in this condition, as well as in SLE. Further research is needed to define the exact relationship between the two conditions.
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