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. 2022 Mar 17;14(6):1544.
doi: 10.3390/cancers14061544.

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)

Sabrina Jotschke  1 , Susann Schulze  1 , Nadja Jaekel  2 , Beatrice Ludwig-Kraus  3 , Robby Engelmann  4 , Frank Bernhard Kraus  3 , Christina Zahn  2 , Nicole Nedlitz  1 , Gabriele Prange-Krex  5 , Johannes Mohm  5 , Bettina Peuser  6 , Maik Schwarz  7 , Claudia Spohn  8 , Timo Behlendorf  9 , Mascha Binder  2 , Christian Junghanss  4 , Sebastian Böttcher  4 , Haifa Kathrin Al-Ali  1   2
Affiliations

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)

Sabrina Jotschke et al. Cancers (Basel). .

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.

Keywords: CD4+-cells; CD8+-cells; SARS-CoV-2 vaccination; T-cells; anti-spike-IgG; lymphoid neoplasms; myeloid neoplasms; seroconversion.

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Conflict of interest statement

A-A.H.K.: Consulting: Novartis, BMS, Takeda, Pfizer, Abbvie; Honoraria: Novartis, BMS, Takeda, Pfizer, Abbvie; Research Funding: Novartis, BMS, Incyte; B.S.: Consulting: Roche, Honoraria Roche, AbbVie, Novartis, AstraZeneca, Amgen, Janssen, Research Funding: Janssen, Miltenyi Biotec, Roche, Genentech, AbbVie; J.C.: Honoraria Novartis, Amgen, Janssen, AbbVie Research Funding: Janssen, Miltenyi Biotec, Roche, Centogene; All other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
CONSORT flowchart of study population.
Figure 2
Figure 2
Humoral anti-spike-specific responses in patients and controls on day 35 and day 120 after vaccination. Specific IgG responses were maintained at high rates in controls (98%) and increased in patients with oncologic malignancies on checkpoint inhibitors (81% to 100%), lymphoid (48% to 66%), and myeloid neoplasms (82% to 97%). A complete loss of the anti-spike IgG was rarely seen.
Figure 3
Figure 3
Correlation between spike-specific CD4 + IL-2 + IFNγ + TNFα + (CovCD4) and CD8 + IL-2 + IFNγ + TNFα + (CovCD8) cell responses (A) and anti-spike IgG concentrations (B,C) on day 120 after vaccination. Results are shown for controls as well as for patients with lymphoid and myeloid neoplasms. Broken lines represent the limit of detection (LOD). Regression lines, Spearman correlation coefficients, and significance are calculated for double positive patients.
See this image and copyright information in PMC

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