Abstract P161: Impaired serological response to SARS-CoV-2 mRNA vaccination in patients with hematologic malignancies
Authors: Greenberger Lee M. , Saltzman Larry A. , Senefeld Jonathon W. , Johnson Patrick W. , DeGennaro Louis J. , Nichols Gwen L. 
Published: December 2021

Although SARS-CoV-2 vaccines induce a robust immune response in healthy individuals, limited reports indicate that some immunocompromised patients may not produce anti-spike antibodies after vaccination. In this report, we assessed anti-spike antibody levels among 2200 patients with hematologic malignancies after SARS-CoV-2 mRNA vaccination (NCT04794387). Diagnoses and treatments were self-reported using a national online registry. The side-effects profile of the vaccines was not different compared to previous studies in healthy individuals. The serological response &gt;14 days after full vaccination was evaluated using the Roche Elecsys total immunoglobulin anti-spike assay (range: 0-250 U/ml; positive cutoff of &gt; 0.8 U/mL). Approximately 40% and 60% were male and females, respectively, 96% were white or Caucasian, and the median age was 67 (range, 21 to 92 years). Patients received the BNT162b (Pfizer/BioNtech: 55%) or mRNA1246 (Moderna: 45%) vaccines. The largest patient populations had chronic lymphocytic leukemia (CLL: N = 978, 44%), multiple myeloma (MM: 253, 11.4%), follicular lymphoma (FL: 147, 6.6%), Waldenstrom’s macroglobulinemia (WM: 115, 5.9%), Hodgkin lymphoma (HL: 79, 3.5%), diffuse large B-cell lymphoma (DLBCL: 83, 3.7%), mantle cell lymphoma (MCL: 58, 2.6%), or marginal zone lymphomas (MZL: 52, 2.3%). Ninety-one patients (3.8%) were positive for the nucleocapsid antibodies and deleted from the initial analysis. Overall, 564 patients (25%) were seronegative after full vaccination. The largest percentages of seronegative patients had B-cell derived hematologic malignancies: MCL (50%), MZL (37%), DLBCL (34%), CLL (32%), FL (28%), and WM (25%). Seronegative rates of 5.9% and 14% were found in patients with multiple myeloma and acute lymphoblastic leukemia, respectively. All but one HL patient and no patients with smoldering multiple myeloma, myeloproliferative neoplasms, myelodysplastic syndrome were seronegative. Anti-spike antibody levels did not markedly change within 35 individual patients &gt;45 days after the initial vaccine assessment except for one patient who seroconverted after a third vaccine dose. High seronegative rates correlated with treatment regimens that contained anti-CD20 mAbs, any Bruton tyrosine kinase inhibitor, and CD19-directed CAR T-therapy. Seronegative rates were higher with the BioNTech/Pfizer vs. Moderna vaccines in an unadjusted analysis (odds ratio, 1.5; 95% confidence interval, 1.05-1.55; p= 0.015). The overall seronegative rate was ~1% among nucleocapsid-positive patients. Among CLL patients, the seronegative rate was lower among nucleocapsid-positive patients compared to nucleocapsid-negative patients (0% vs. 32%, p&lt;0.001). Providers should be aware that a substantial subset of vaccinated blood cancer patients may be at high risk of breakthrough COVID-19 infections. Alternate therapies with monoclonal antibodies or booster vaccination including those that would allow exposure to more than the spike protein, may offer additional protection for this vulnerable population.

Citation Format: Lee M. Greenberger, Larry A. Saltzman, Jonathon W. Senefeld, Patrick W. Johnson, Louis J. DeGennaro, Gwen L. Nichols. Impaired serological response to SARS-CoV-2 mRNA vaccination in patients with hematologic malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P161.