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4618 Sars-Cov-2 Vaccine-Induced Cellular and Humoral Immunity in Patients after CD19.CAR-T Cell TherapyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Research, Translational Research, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, real-world evidence, Therapies, immunology, Biological Processes, Vaccines
Monday, December 12, 2022, 6:00 PM-8:00 PM

Hannah Reimann, PhD1*, Anita Natalie Kremer, MD, PhD2*, Viktoria Blumenberg, MD3,4,5, Katja Schmidt6*, Michael Aigner, PhD7*, Andreas Kremer, MD, PhD8,9*, Matthias Tenbusch10*, Heiko Bruns, PhD2*, Thomas Harrer6*, Georg Schett, MD11*, Fabian Mueller, MD7*, Andreas Mackensen, MD12*, Marion Subklewe, MD13,14,15 and Simon Voelkl, PhD7*

1Department of Internal Medicine 5 - Hematology/Oncology, University Hospital Erlangen, Erlangen, DEU
2Department of Internal Medicine 5 - Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany
3Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany
4Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
5German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Munich, Heidelberg, Germany
6Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital Erlangen, Erlangen, Germany
7Department of Internal Medicine 5 - Hematology/Oncology, University Hospital of Erlangen, Erlangen, Germany
8Department of Gasteroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
9Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, DEU
10Institute of Clinical and Molecular Virology, University Hospital Erlangen, Erlangen, Germany
11Department of Internal Medicine 3, University Hospital of Erlangen, Erlangen, Germany
12Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany
13German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
14Department of Medicine III (Hematology/Oncology), LMU University Hospital Munich, Muenchen, Germany
15Laboratory for Translational Cancer Immunology, Gene Center, LMU Munich, Munich, Germany

Introduction: Chimeric antigen receptor T (CAR-T) cell therapies that target CD19 have advanced the treatment of relapsed or refractory B cell malignancies. However, patients are often long-term depleted of conventional B cells and presumably do not develop humoral immunity after vaccination. Despite high efficacy of SARS-CoV-2 vaccination as shown in millions of people worldwide, the benefit for patients undergoing CD19.CAR-T cell therapy still remains elusive.

Methods: We determined the humoral and cellular immune responses to SARS-CoV-2 vaccination in 15 patients after CD19.CAR-T cell therapy. In addition, we analyzed 21 patients that were vaccinated before undergoing lymphodepletion and CD19.CAR-T cell treatment for sustained anti-SARS-CoV-2 immunity. Peripheral blood samples were taken before and after SARS-CoV-2 vaccination or before and after CD19.CAR T-cell therapy. Sera were analyzed for the presence of anti-Spike and neutralizing antibodies. SARS-CoV-2 specific T cells were detected by flow cytometric analysis of activation markers with or without prior in vitro stimulation with SARS-CoV-2 Spike and Nucleocapsid antigen.

Results: First, we analyzed 15 patients that previously received CD19.CAR T cells for development of SARS-CoV-2 specific antibodies after vaccination. 13 of 15 patients were still completely B-cell depleted at the time of vaccination, circulating CD19.CAR-T cells could be detected in 10 patients. Only two of the patients showed seroconversion and neutralizing antibodies after vaccination, but most of these patients (13 out of 15) developed Spike-specific T cell responses. Furthermore, we tested 21 patients vaccinated before undergoing lymphodepletion and CD19.CAR-T cell therapy. Interestingly, humoral immune responses remained predominately unchanged in previously vaccinated CD19.CAR-T cell treated patients. Thus, all 10 previously seropositive patients remained positive for S-specific and neutralizing antibodies and 10 of 11 seronegative remained negative. One patient seroconverted which might be explained by an unrecognized infection. Moreover, in patients vaccinated before receiving CD19.CAR-T cells the cellular immune response was sustained throughout the treatment with a constant T-cell response rate.

Conclusions: Taken together, our data confirm strong cellular immune responses to SARS-CoV-2 vaccination in a majority of patients with severe B cell depletion after CD19.CAR-T cell therapy. Since most patients vaccinated before CD19.CAR-T cell treatment showed a humoral and cellular immune response, our study provides evidence for vaccination before CD19.CAR-T cell therapy with subsequent antibody-response detection.

Disclosures: Kremer: Bayer: Current Employment. Blumenberg: Novartis: Honoraria, Research Funding; Celgene: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Research Funding. Harrer: GSK: Consultancy. Mackensen: Novartis: Honoraria; BMS/Celgene: Honoraria; Miltenyi Biomedicine: Honoraria; Kite/Gilead: Honoraria. Subklewe: Roche: Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Miltenyi Biotech: Consultancy, Research Funding; Seagen: Research Funding; MorphoSys: Research Funding; Amgen: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau; Ichnos: Consultancy; Pfizer: Consultancy, Speakers Bureau; BMS/Celgene: Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; AvenCell: Consultancy; CDR-Life: Consultancy; Incyte: Consultancy; Molecular Partners: Consultancy.

*signifies non-member of ASH