Longitudinal Vaccine-Induced Humoral Immune Response in Cancer Patients

Abstract

Background: Longitudinal studies of mRNA vaccine-induced response demonstrate robust protection up to six months in healthy patients; however, evaluation of sustained response in cancer patients are lacking.Methods: In a prospective cohort study, 366 (291 vaccinated) patients [171 (145) solid tumors, 195 (146) hematologic malignancies] were enrolled and followed from November 2020 through September 2021. Antibody levels [anti-spike (IgG-(S-RBD)) and anti-nucleocapsid (IgG-N) immunoglobulin] were measured at three timepoints. Trajectories, peak, and persistence of antibody levels over time and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination.Findings: At peak response (median=42 days after dose 1, interquartile range =26–57), 87.0% and 90.2% of patients were seropositive after two-dose BNT162b2 and mRNA-1273 vaccination (median IgG-(S-RBD)= 2,259 v. 9,804 AU/ml, p=0.002), respectively. Antibody response persisted longer in cancer patients receiving mRNA-1273 compared to BNT162b2 (p=0.003). Overall, patients with solid tumors attained higher peak (8,323 v. 1,128 AU/ml, p=0.001) and sustained antibody levels after 4–6 months (1,637 v. 353 AU/ml, pInterpretation: Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities with important implications for vaccine booster timing and patient selection.Funding: NCI U54CA260591; NIH P01DK046763; NIH U01DK062413; K23HL153888; Cedars-Sinai Medical Center; Cedars-Sinai Precision Health Initiative; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute; the Erika J. Glazer Family Foundation; and The Leona M. and Harry B. Helmsley Charitable Trust.Declaration of Interest: NM holds a consultant or advisory role at Amgen, Kite, Epizyme, TG Therapeutics, ADC Therapeutics, and has research funding from Miltenyi, Teva, and Amgen. JG holds a consultant or advisory role at EMD Serono; Elsevier; Exelixis; QED Therapeutics; Natera, Basilea, HalioDx, Eisai, Janssen. KR holds a consultant or advisory role at Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, Daiichi Sankyo, EMD Soreno, Genentech, GSK, Janssen, Lilly, Merck KGA, Mirati, Seattle Genetics, Takeda. JD holds a consultant or advisory role Kite Pharma and Morphosys. RB holds a consultant or advisory role at Genomic Health, Astra Zeneca, Biotheranostics, Pfizer; She is on the Speakers Bureau for Genentech, Seattle Genetics; she has research funding from Seattle Genetics, Ichnos Biosciences, Merck. JB has received research funding from Janssen. GYM has consulted for AbbVie, Arena Pharmaceuticals, Boehringer-Ingelheim, Bristol-Meyers Squibb/Celgene, Entasis, Janssen, Medtronic, Pfizer, Samsung Bioepis, Shionogi, Takeda, Techlab, and has received research funding from Pfizer for an unrelated investigator-initiated study. RV is on the Speaker’s Bureau for: Amgen, Bristol Myers Squib, Glaxo Smith Klein, Janssen, Karyopharm, and Takeda Pharmaceuticals. DM holds a consultant role for Prometheus Biosciences, Prometheus Laboratories, Pfizer, Takeda, Gilead, Palatin Technologies, and is a shareholder for Prometheus Biosciences. AM holds a consultant or advisory role at Novartis and Morphosys and has research funding from Amgen and Pfizer. All remaining authors have no COI to report.Ethical Approval: The study was approval by the institutional review board and all participants provided written informed consent.