RESUMEN
PURPOSE: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity. METHODS: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune microenvironment to predict disease control with monotherapy PD-1 inhibitors (pembrolizumab and nivolumab). The performance of the biomarker was internally validated using out-of-bag methods. RESULTS: The biomarker significantly predicted disease control (65% in predicted non-progressors vs. 17% in predicted progressors, p < 0.001) and was significantly correlated with overall survival (OS; p = 0.004). In addition, the biomarker outperformed PD-L1 IHC across numerous metrics including sensitivity (0.79 vs 0.64, respectively; p = 0.005) and specificity (0.70 vs 0.61, respectively; p = 0.009). CONCLUSION: This novel assay uses tumor immune microenvironment expression data to predict disease control and OS with high sensitivity and specificity in patients with RM-HNSCC treated with anti-PD-1 monotherapy.
RESUMEN
PURPOSE: To report a case of severe immune-mediated thrombocytopenia after intravitreal bevacizumab administration. METHODS: A 77-year-old man with right-sided macular degeneration received intravitreal bevacizumab. After his third treatment dose, he was hospitalized for symptomatic thrombocytopenia (platelet count of 3 k/µL) and underwent testing to determine the etiology. RESULTS: Initial platelet counts on admission were 3 k/µL, down from 238 k/µL 3 months before. A peripheral smear, coagulation studies, and an abdominal CT were unremarkable. A bone marrow biopsy revealed hypercellular marrow with megakaryocytic hyperplasia. Serum antiplatelet antibody testing identified antibodies against glycoprotein IV and human leukocyte antigens. A total of 13 units of platelets were administered and resulted in no significant response. Treatment with rituximab, romiplostim, and human leukocyte antigen-matched platelets resulted in slow recovery and normalization of platelet counts. CONCLUSION: The case presented shows apparent severe immune-mediated thrombocytopenia after intravitreal bevacizumab administration.
