Longitudinal Humoral and Cellular Immune Responses Following SARS-CoV-2 Vaccination in Patients with Myeloid and Lymphoid Neoplasms Compared to a Reference Cohort: Results of a Prospective Trial of the East German Study Group for Hematology and Oncology (OSHO)

SIMPLE SUMMARY: The kinetics of SARS-CoV-2 spike-protein antibodies and the cellular immune landscape following vaccination in patients with hematologic neoplasms are poorly understood. The aim of our prospective and longitudinal study, which included 398 adults, was to compare day 35 and day 120 anti-spike-IgG antibody and day 120 SARS-CoV-2-specific T-cell responses in patients with hematologic malignancies to a reference cohort. Although day 35 seroconversion in controls (98%) was higher compared to patients with myeloid (82%) and lymphoid (48%) neoplasms, substantial increases in day 120 seroconversion were seen in both the myeloid (97%) and lymphoid (66%) cohorts. Remarkably, spike-specific CD4(+)- and CD8(+)-cells in the lymphoid (71%/31%) and control (74%/42%) cohorts were comparable. We provide strong evidence of vaccine-elicited immunogenicity in most patients with hematologic malignancies. Both kinetics of seroconversion and cellular responses are crucial to determine which patients with hematologic malignancies will generate immunity. The findings have implications on public health policy regarding recommendations for SARS-CoV-2 booster doses. ABSTRACT: Purpose: To assess humoral responses longitudinally and cellular immunogenicity following SARS-CoV-2-vaccination in patients with hematologic and oncologic malignancies receiving checkpoint-inhibitors. Methods: This prospective multicenter trial of the East-German-Study-Group-for-Hematology-and-Oncology, enrolled 398 adults in a two (patients; n = 262) to one (controls; n = 136) ratio. Pre-vaccination, day 35 (d35), and day 120 (d120) blood samples were analyzed for anti-spike antibodies and d120 IL-2(+)IFNγ(+)TNFα(+)-CD4(+)- and CD8(+)-cells. Laboratories were blinded for patients and controls. Results: Patients belonged to the myeloid (n = 131), lymphoid (n = 104), and checkpoint-inhibitor (n = 17) cohorts. While d35 seroconversion was higher in controls (98%) compared to patients (68%) (p < 0.001), d120 seroconversion improved across all patient cohorts [checkpoint-inhibitors (81% to 100%), myeloid (82% to 97%), lymphoid (48% to 66%)]. CD4(+)- and CovCD8(+)-cells in the lymphoid (71%/31%) and control (74%/42%) cohorts were comparable but fewer in the myeloid cohort (53%, p = 0.003 /24%, p = 0.03). In patients with hematologic malignancies, no correlation between d120 humoral and cellular responses was found. A sizeable fraction of lymphoid patients demonstrated T-cell responses without detectable spike-specific-IgGs. Conclusions: Evidence of vaccine-elicited humoral and/or cellular immunogenicity in most patients is provided. Both humoral and cellular responses are crucial to determine which patients will generate/maintain immunity. The findings have implications on public health policy regarding recommendations for SARS-CoV-2 booster doses.