Thursday, March 23, 2023
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The data regarding COVID-19 vaccination are constantly evolving, and one of the most salient questions now focuses on the application of a fourth dose of messenger RNA (mRNA)-based vaccination among middle-aged and older adults. Magen and colleagues addressed this issue in a study published in the April 28, 2022 issue of the New England Journal of Medicine.[1]
Researchers compared the clinical efficacy of a fourth dose of BNT162b2 (Pfizer-BioNTech) with a course of 3 doses, with the third dose provided at least 4 months previously. All study patients were aged at least 60 years. The study period extended from January 3 to February 18.
Relative vaccine effectiveness of the fourth dose in days 7 to 30 after vaccination was 45% against lab-confirmed infection with SARS-CoV-2; 55% against symptomatic COVID-19; 68% against COVID-19--related hospitalization; 62% against severe COVID-19; and 74% against death related to COVID-19. The absolute risk reduction associated with the fourth dose were 180.1 cases per 100,000 persons for COVID-19--related hospitalization and 68.8 cases per 100,000 persons for severe COVID-19.
One important group of patients for vaccination includes those undergoing active treatment for cancer or with a history of stem cell transplant. The current study by Khan and colleagues addresses COVID-19 vaccine efficacy in this population.
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, "indicative of a brisk anamnestic response from memory B cells," Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, Missouri, and colleagues reported.
The study appeared online April 21 in JAMA Oncology.[2]
Given the risk for poor outcomes among patients with cancer and recipients of SCTs who get COVID-19, Khan and colleagues wanted to understand the durability of the antibody response to COVID-19 vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors, and 30% had hematologic malignancies. About 40% were receiving chemotherapy, 17% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 35% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Before vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 two weeks after the first dose.
At one month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 six months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9224.85 -- more than 20 times the previous GMT value.
According to the investigators, approximately 80% of these patients remained above the threshold of an anti-RBD level of ≥ 100 U/mL at 6 months.
"While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant," Khan and colleagues wrote.
"Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources," the authors concluded.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Khan reported no relevant financial relationships. A complete list of author disclosures is available with the original article.
