Partial Response to Naxitamab for Brain Metastasis in Neuroblastoma.

Neuroblastoma (NBL) is a common pediatric tumor arising from sympathetic ganglion cells. High-risk NBL is based on age, stage, histology, and MYCN amplification, and is associated with a high mortality rate. The combination of naxitamab (NAX) and granulocyte-macrophage (cerebrospinal fluid) is a new treatment for high-risk and relapsed NBL approved for bone or bone marrow disease. NAX is a monoclonal antibody directed against anti-disialoganglioside, which is overexpressed in neuroblastoma. Under normal circumstances, monoclonal antibodies, such as NAX, cannot cross the blood-brain barrier due to size. We present the case of a patient with high-risk NBL treated with NAX for multiple bony relapses. Unexpectedly, her brain metastasis responded clinically, histologically, and by imaging to the treatment. We believe this is the first documented case of NBL of the brain responding to NAX.

Immune Dysregulation in Acute SARS-CoV-2 Infection.

Introduction: Neutralizing antibodies have been shown to develop rapidly following SARS-CoV-2 infection, specifically against spike (S) protein, where cytokine release and production is understood to drive the humoral immune response during acute infection. Thus, we evaluated the quantity and function of antibodies across disease severities and analyzed the associated inflammatory and coagulation pathways to identify acute markers that correlate with antibody response following infection. Methods: Blood samples were collected from patients at time of diagnostic SARS-CoV-2 PCR testing between March 2020-November 2020. Plasma samples were analyzed using the MesoScale Discovery (MSD) Platform using the COVID-19 Serology Kit and U-Plex 8 analyte multiplex plate to measure anti-alpha and beta coronavirus antibody concentration and ACE2 blocking function, as well as plasma cytokines. Results: A total of 230 (181 unique patients) samples were analyzed across the 5 COVID-19 disease severities. We found that antibody quantity directly correlated with functional ability to block virus binding to membrane-bound ACE2, where a lower SARS-CoV-2 anti-spike/anti-RBD response corresponded with a lower antibody blocking potential compared to higher antibody response (anti-S1 r = 0.884, P < 0.001; anti-RBD r = 0.75, P < 0.001). Across all the soluble proinflammatory markers we examined, ICAM, IL-1ß, IL-4, IL-6, TNFα, and Syndecan showed a statistically significant positive correlation between cytokine or epithelial marker and antibody quantity regardless of COVID-19 disease severity. Analysis of autoantibodies against type 1 interferon was not shown to be statistically significant between disease severity groups. Conclusion: Previous studies have shown that proinflammatory markers, including IL-6, IL-8, IL-1ß, and TNFα, are significant predictors of COVID-19 disease severity, regardless of demographics or comorbidities. Our study demonstrated that not only are these proinflammatory markers, as well as IL-4, ICAM, and Syndecan, correlative of disease severity, they are also correlative of antibody quantity and quality following SARS-CoV-2 exposure.