Third dose of COVID-19 vaccine effective for immunocompromised patients with blood cancers
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Key takeaways:
- Three mRNA vaccine doses resulted in significantly higher concentrations of anti-spike antibodies similar to those seen in healthy adults who received two standard doses.
- Seventy percent of patients with low responses to the first two doses of vaccine had S1-IgG concentrations of 300 BAU/mL or greater.
- COVID-19 vaccination in immunocompromised patients with hematologic cancers should be based on a three-dose mRNA-1273 schedule.
A third dose of the mRNA-1273 vaccine for COVID-19 significantly improved SARS-CoV-2 antibody concentrations among patients with hematologic malignancies who previously received two doses, results of a prospective study showed.
In the study, published in JAMA Oncology, most immunocompromised patients with hematologic malignancies who received a third dose of the mRNA-1273 (Moderna) vaccine had antibody concentrations similar to healthy control patients who received the standard two-dose regimen.
Based on the results, the investigators suggested a standard three-dose regimen of the vaccine for immunocompromised patients with hematologic malignancies instead of the two-dose regimen recommended for healthy individuals.
Background
Previous studies have shown that patients with hematologic malignancies have inferior responses to COVID-19 vaccines, with reduced immunogenicity the result of both disease effects and the therapies used for treatment, Sabine Haggenburg, MD, of Amsterdam University Medical Center, and colleagues, noted.
“It has become common practice to offer immunocompromised patients with hematologic cancers a third vaccination to improve SARS-CoV-2 immunity to levels obtained in healthy individuals after the standard two-dose vaccination schedule, but data substantiating this are lacking,” they wrote.
Methodology
Haggenburg and colleagues conducted a prospective observational cohort study of 584 adults (mean age, 60 ± 11.2 years; 63% men) with compromised immune systems and a hematologic malignancy treated at one of four university hospitals in the Netherlands. The cohort included patients with lymphoma, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, acute myeloid leukemia and myeloproliferative disease.
All patients completed a three-dose schedule of the mRNA vaccine that included a third dose given 5 months after completion of the standard two-dose regimen.
The study also included a randomly selected, age-matched comparison cohort of 44 healthy adults with no known malignant or immunodeficient comorbidities.
Evaluation of humoral responses against spike glycoprotein and nucleoprotein of the SARS-CoV-2 virus before and 28 days after each mRNA-1273 vaccination served as the study’s primary endpoint. The study also evaluated the antibody neutralization of vaccines against wild-type COVID-19 and selected variants in a subgroup of patients.
Investigators determined an adequate response to vaccination as spike glycoprotein-immunoglobulin-G (S1-IgG) concentration of 300 binding antibody units (BAU)/mL or greater.
Key findings
A third dose of the mRNA vaccine resulted in significantly higher concentrations of anti-spike antibodies that were comparable to antibody levels seen in healthy adults who received two standard doses.
Patients with lymphoma receiving anti-CD20 therapy or CD19-directed chimeric antigen receptor T cells and patients with chronic lymphocytic leukemia receiving ibrutinib (Imbruvica; Janssen, Pharmacyclics) did not respond as well to a third vaccine dose.
Seroconversion rates improved from 68.9% after the second dose to 78.8% after the third dose of mRNA vaccine among immunocompromised patients with hematologic malignancies.
Seventy percent of patients who had a low response to the first two doses of vaccine had S1-IgG concentrations of 300 BAU/mL or greater after the third dose.
Investigators found a significant association between serum S1-IgG concentrations after the third vaccination and neutralization of SARS-CoV-2 wild-type (D614G; r = .95; P < .001), the delta B.1.617.2 variant (r = .90; P < .001) and the omicron BA.1 variant (r = .88; P < .001).
Clinical implications
“In this study, we demonstrate that following a third mRNA-1273 vaccination, the majority of immunocompromised patients with hematologic cancers obtained SARS-CoV-2 antibody concentrations similar to healthy individuals after the standard two-dose mRNA-1273 schedule,” Haggenburg and colleagues wrote. “Results of this cohort study suggest that COVID-19 vaccination in immunocompromised patients with hematologic cancers should be based on a three-dose mRNA-1273 schedule.”
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