In a Dutch prospective observational cohort study reported in JAMA Oncology, Haggenburg et al found that a third dose of the COVID-19 mRNA-1273 vaccine increased antibody levels in immunocompromised patients with hematologic cancers overall to levels comparable to those observed in healthy controls after the standard two-dose schedule. Antibody response to the third dose was poor in some subgroups.
The investigators stated, “It has become common practice to offer immunocompromised patients with hematologic cancers a third COVID-19 vaccination dose, but data substantiating this are scarce.”
Study Details
The multicenter study included 584 patients with a range of hematologic cancers who received an additional mRNA-1273 vaccination 5 months after completion of the standard two-dose schedule and 44 randomly selected age-matched healthy controls who had received the standard two-dose schedule. Serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens were measured prior to and 4 weeks after the third mRNA-1273 vaccination in patients.
Results of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.— Haggenburg et al
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Key Findings
At 5 months after completion of the standard two-dose mRNA-1273 schedule, S1-IgG concentrations had declined significantly to a median of 92.5 binding antibody units (BAU)/mL, with 33.9% of patients maintaining S1-IgG concentration of ≥ 300BAU/mL. The third dose was associated with a significant increase in S1-IgG concentration; median levels in patients vs controls were 2,171.3 vs 1,566.5 BAU/mL (P = .46) and 67.3% of patients achieved levels of ≥ 300 BAU/mL.
The third dose was associated with significant increases in S1-IgG concentration in most patient groups. However, patients with B-cell non-Hodgkin lymphoma with ongoing B-cell depletion due to CD20 monoclonal antibody or chimeric antigen receptor T-cell therapy and patients with chronic lymphocytic leukemia receiving ibrutinib were less responsive or unresponsive to the third dose.
The greatest median increases in S1-IgG concentrations were observed in patients with a recovering immune system: 36-fold for patients receiving CD20 antibody therapy < 12 months prior to the first vaccination, 15-fold for those with B-cell non-Hodgkin lymphoma who had received autologous hematopoietic cell transplantation (HCT) < 12 months prior to the first vaccination, and 49-fold in those who had received allogeneic HCT < 6 months before the first vaccination.
Significant increases were also observed in patients with ongoing immunodeficiencies, including patients with acute myeloid leukemia or myelodysplastic syndrome receiving hypomethylating therapy, those with myeloproliferative neoplasms receiving ruxolitinib, and those with chronic graft-vs-host disease receiving immunosuppressive therapy.
In a subgroup study of antibody neutralization capacity of wild-type, Delta, and Omicron variants, the third vaccination was associated with significantly improved neutralization capacity per antibody.
The investigators concluded, “Results of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.”
Mette D. Hazenberg, MD, PhD, of the Department of Hematology, Amsterdam UMC, University of Amsterdam, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Dutch Research Council and Amsterdam UMC. For full disclosures of the study authors, visit jamanetwork.com.
