Sars-Cov-2 Vaccine-Induced Cellular and Humoral Immunity in Patients after CD19.CAR-T Cell Therapy

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.

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:Takeda: Other: Travel support; Miltenyi Biotech: Research Funding; Roche: Consultancy, Research Funding; Seattle Genetics: Research Funding; Celgene/BMS: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Janssen: Consultancy, Speakers Bureau; Morphosys: Research Funding; Seagen: Research Funding; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau.