Jay Yaakov Spiegel
Postdoctoral Medical Fellow, Bone Marrow Transplantation
Fellow in Medicine
Fellow in Medicine
Stanford Advisors
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Wen-Kai Weng, Postdoctoral Faculty Sponsor
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David Miklos, Postdoctoral Research Mentor
All Publications
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Outcomes of Patients with Large B-cell Lymphoma Progressing after Axicabtagene Ciloleucel.
Blood
2020
View details for DOI 10.1182/blood.2020006245
View details for PubMedID 33156925
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Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET.
Clinical cancer research : an official journal of the American Association for Cancer Research
2020
Abstract
PURPOSE: Immunomonitoring of chimeric antigen receptor (CAR) T cells relies primarily on their quantification in the peripheral blood, which inadequately quantifies their biodistribution and activation status in the tissues. Non-invasive molecular imaging of CAR T cells by positron emission tomography (PET) is a promising approach with the ability to provide spatial, temporal and functional information. Reported strategies rely on the incorporation of reporter transgenes or ex vivo biolabeling, significantly limiting the application of CAR T cell molecular imaging. In the present study, we assessed the ability of antibody-based PET (immunoPET) to non-invasively visualize CAR T cells.EXPERIMENTAL DESIGN: After analyzing human CAR T cells in vitro and ex vivo from patient samples to identify candidate targets for immunoPET, we employed a syngeneic, orthotopic murine tumor model of lymphoma to assess the feasibility of in vivo tracking of CAR T cells by immunoPET using the 89Zr-DFO-anti-ICOS tracer we previously reported.RESULTS: Analysis of human CD19-CAR T cells during activation identified the Inducible T-cell COStimulator (ICOS) as a potential target for immunoPET. In a preclinical tumor model, 89Zr-DFO-ICOS mAb PET-CT imaging detected significantly higher signal in specific bone marrow-containing skeletal sites of CAR T cell treated mice compared with controls. Importantly, administration of ICOS-targeting antibodies at tracer doses did not interfere with CAR T cell persistence and function.CONCLUSIONS: This study highlights the potential of ICOS-immunoPET imaging for monitoring of CAR T cell therapy, a strategy readily applicable to both commercially available and investigational CAR T cells.
View details for DOI 10.1158/1078-0432.CCR-20-2770
View details for PubMedID 33087332
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Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2020: JCO1902104
Abstract
PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication.PATIENTS AND METHODS: Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution's guidelines. Responses were assessed as per Lugano 2014 classification.RESULTS: Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel-treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis.CONCLUSION: The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.
View details for DOI 10.1200/JCO.19.02104
View details for PubMedID 32401634
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Outcomes Following Failure of JAK 1/2 Inhibitor Therapy in Patients with Myelofibrosis is Dependent on the Pattern of Failure
CIG MEDIA GROUP, LP. 2019: S351–S352
View details for DOI 10.1016/j.clml.2019.07.366
View details for Web of Science ID 000483480700397
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Monitoring ctDNA in r/r DLBCL patients following the CAR T-cell therapy axicabtagene ciloleucel: Day 28 landmark analysis.
AMER SOC CLINICAL ONCOLOGY. 2019
View details for Web of Science ID 000487345806314
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Utilization of value stream mapping to improve chimeric antigen receptor (CAR) T-cell patient experience at an academic medical center (AMC).
AMER SOC CLINICAL ONCOLOGY. 2019
View details for DOI 10.1200/JCO.2019.37.15_suppl.6607
View details for Web of Science ID 000487345806161
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Outcomes in large B-cell lymphoma progressing after axicabtagene ciloleucel (Axi-cel): Results from the US Lymphoma CAR-T Consortium.
AMER SOC CLINICAL ONCOLOGY. 2019
View details for Web of Science ID 000487345806279
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Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-113261
View details for Web of Science ID 000454837601285
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Target Antigen Downregulation and Other Mechanisms of Failure after Axicabtagene Ciloleucel (CAR19) Therapy
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-120206
View details for Web of Science ID 000454842804282
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Phase I Experience with a Bi-Specific CAR Targeting CD19 and CD22 in Adults with B-Cell Malignancies
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-110142
View details for Web of Science ID 000454837601199
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Axicabtagene Ciloleucel (Axi-cel) CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Real World Experience
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-114152
View details for Web of Science ID 000454837600145