Added new papers

papers/_posts/2025-05-13-anakinra-prophylaxis-cart.md

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+---
+layout: paper
+title: "Single-cell dynamics of breakthrough toxicities after anakinra prophylaxis for axicabtagene ciloleucel in lymphoma"
+year: "2025"
+journal: Blood Advances
+authors: Frigault MJ, Yao N, Berger TR, Wehrli M, Gallagher KME, Horick N, Graham CE, Jacobson CA, Chen YB, Leick MB, DeFilipp Z, El-Jawahri AR, Johnson PC, Dolaher M, Katsis K, Kim AI, Crombie J, Merryman RW, Cook D, Trailor M, Cho H, Jeffrey 3rd R, Shen R, Filosto S, Nater J, Getz G, Haradhvala NJ, Maus MV
+first_authors: Frigault MJ, Yao N
+senior_authors: Getz G, Haradhvala NJ, Maus MV
+corresponding_authors: 
+fulltext: https://ashpublications.org/bloodadvances/article/9/9/2122/535555/Single-cell-dynamics-of-breakthrough-toxicities
+pdflink: https://watermark02.silverchair.com/blooda_adv-2024-015161-main.pdf
+doi: 10.1182/bloodadvances.2024015161
+pmid: 39928957
+category: paper
+---
+
+
+# Abstract
+Chimeric antigen receptor T (CAR-T) cell therapy is limited by cytokine release syndrome (CRS) and neurotoxicity (NT). We sought to use once-daily prophylactic anakinra, an IL-1R antagonist, to prevent CRS/NT that would require hospitalization (grade 2 or higher) in patients receiving axicabtagene ciloleucel for large cell lymphoma, with the goal of facilitating outpatient therapy and management. Our study (ClinicalTrials.gov #NCT04150913), in line with others, demonstrated that once-daily prophylactic anakinra is insufficient to prevent the development of toxicities that would require hospitalization in most of these patients. As part of the initial study design, we prospectively incorporated scRNAseq to gain insight into the molecular immune signaling associated with breakthrough CRS & NT despite anakinra prophylaxis. In patients who developed breakthrough CRS or NT, we found that IFNg pathways and ligand-receptor activities were significantly enriched, as were cytokine levels of IFNg and CXCL10 in CD14+ monocytes. This correlated with increased IFNg and other cytokines in the peripheral blood. In infused CAR-T products, IL-4 and IL-10 anti-inflammatory pathways were negatively associated with grade 2+ toxicities, regardless of anakinra treatment. These data identify IFNg as a potential key mechanism in CAR-T cell-associated toxicities, which is not inhibited by anakinra but may be otherwise targetable.

papers/_posts/2025-10-21-hnsc-cetux-nivo.md

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+---
+layout: paper
+title: "Long-term Survival and Molecular Biomarker Evaluation of a Phase II Cetuximab and Nivolumab Clinical Trial in Recurrent/Metastatic Head and Neck Cancer"
+year: "2025"
+journal: Clin Cancer Res.
+authors: Chaudhary R, Moorhead G, Park R, Li J, Schell MJ, Song X, Tan A, Slebos RJC, Biernacki MI, Freeman SS, Thatikonda S, Meshkovska Y, Hernandez-Prera J, Kirtane K, Guevara-Patino JA, Amelio AL, Rocco JW, Danysh BP, Bonomi M, Saba NF, Haradhvala NJ, Getz G, Chung CH
+first_authors: Chaudhary R, Moorhead G
+senior_authors: Haradhvala NJ, Getz G, Chung CH
+corresponding_authors: 
+fulltext: https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-25-2201/767240/Long-term-Survival-and-Molecular-Biomarker
+pdflink: 
+doi: 10.1158/1078-0432.CCR-25-2201
+pmid: 41117857
+category: paper
+---
+
+
+# Abstract
+Purpose: We report long-term survival and comprehensive molecular biomarker analyses of a phase II trial evaluating the combination of cetuximab and nivolumab in R/M HNSCC.
+
+Patients and methods: The long-term follow up data were obtained from a phase II trial (NCT03370276). Archived tumors and serially collected plasma cell-free DNA were characterized by comprehensive genomic analyses. Immune markers were measured in tumor core and margins by multiplex immunohistochemistry (mIHC).
+
+Results: At a median follow-up of 47.4 months, median overall survival (OS) and 2-year OS rate were 12.7 months and 32% in all evaluable patients (n=88) and 17.5 months and 35% in patients who had no prior therapy for R/M HNSCC (n=43), respectively. The survival efficacy was similar between patients with p16-negative and p16-positive tumors, but the response rate was significantly higher in patients with p16-negative tumors. The clonal tumor mutation burden, hypoxia score, and EGFR pathway score were significantly higher in p16-negative compared to p16-positive tumors. Loss of heterozygosity of MHC-I was significantly more frequent in non-responders, and APOBEC-associated mutagenesis was elevated in responders. Gene expression profiling and mIHC analyses revealed a more inflamed tumor microenvironment in responders regardless of the p16 status.
+
+Conclusions: Our long-term follow-up study indicates that the combination of cetuximab and nivolumab is efficacious and tolerable, and that p16-negative R/M HNSCC patients may have greater benefit from this combination.