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Patients with hematologic malignancies may be at a higher risk for breakthrough infections following full COVID-19 vaccination.
Patients with hematologic cancer are at risk for not producing antibodies following 2 doses of the COVID-19 vaccine and could be at a high risk for breakthrough infections, according to findings from a prospective cohort registry study (NCT04794387) published in Cancer Cell.1
Estimates from the Leukemia & Lymphoma Society (LLS) indicate that approximately 250,000 patients with hematologic malignancies within the United States will not have detectable antibodies following full vaccination with the COVID-19 vaccine. Additionally, findings from the analysis indicated that 75% of patients with hematologic malignancies produced antibodies against COVID-19 following full vaccination. Notably, patients with common B-cell malignancies had the lowest rate of seropositivity (range, 44%-79%). Overall, the seroconversion rate in patients with hematologic malignancies ranged from 46% to 85% following inoculation with both vaccines. Among a cohort of age- and sex-matched immunocompetent controls, the serological response was 100%.
“Although some patients with hematologic malignancies will not mount a full antibody response compared to healthy individuals, vaccines are safe and offer protection to the majority of blood cancer patients,” Gwen Nichols, chief medical officer at the LLS, said in a press release.2 “But not everyone will be protected, and [patients with] blood cancer are at increased risk of serious illness and death from COVID-19. We encourage blood cancer patients to take every measure to protect themselves from COVID-19 by getting vaccinated and continuing to take preventative precautions. This includes wearing a mask, social distancing, and avoiding crowds and poorly ventilated indoor spaces.”
Investigators pulled samples for the study from March 2021 to May 5, 2021. Fourteen-day antibody response was evaluated in 1495 patients who had received the second dose of the vaccine. The median patient age was 68 years (range, 16-110). In total, 652 patients received mRNA-1246 and 793 received BNT162b2 vaccines.
Additional findings from the study indicated that seronegativity was observed in nearly all patients with non-Hodgkin lymphoma, while 64 patients with Hodgkin lymphoma were seropositive. Seronegativity was also noted in 56% of patients with mantle cell lymphoma (MCL), 38% of those with marginal zone lymphoma, 26% of those with Waldenström macroglobulinemia, 22% of those with follicular lymphoma, and 21% of those with diffuse large B-cell lymphoma. Investigators reported that seronegativity was observed in those who had received no therapy within the past 2 years and those who had previously been treated with a number of B-cell–suppressive therapies, including anti-CD20 monoclonal antibodies, BTK inhibitors, and CD19 CAR T-cell therapy.
Moreover, of the 36% of patients with chronic lymphocytic leukemia (CLL) who did not generate spike antibodies, 66 of 235 patients reportedly did not receive therapy within the last 2 years. Investigators believe that disease may directly impair B-cell function. Additionally, high seronegative rates were noted among patients who were receiving treatment with BTK inhibitors, anti-CD20 monoclonal antibodies, or those who received a combination of the aforementioned therapies plus venetoclax (Venclexta).
Conversely, patients with acute myeloid leukemia, acute lymphocytic leukemia, and CLL had seronegativity rates of 9%, 12%, and 2.9%, respectively, as well as 5.3% of those with multiple myeloma. However, no patients with smoldering myeloma were reported as being seronegative.
Investigators assessed differences in response between both COVID-19 vaccines within a population of seronegative malignancies, including MCL, follicular lymphoma, and Waldenström macroglobulinemia (n = 845). The unadjusted logistic regression analysis found patients were more likely to mount an immune response to the mRNA-1273 vaccine vs the BNT162b2 vaccine (OR, 1.50; 95% CI, 1.06-2.06; P = .021; OR, 1.73; 95% CI, 1.12-2.42; P = .001). This was further supported by the regression model with adjustments for age, disease type, gender, vaccine, and cancer group utilizing 2 different models (OR, 1.48; CI, 1.06-2.06; P = 0.021; OR, 1.73; CI, 1.24-2.42; P = 0.001).
“Many patients with hematologic malignancies are at risk of not producing antibodies after two doses of the mRNA SARS-CoV-2 vaccines. Differences in antibody responses between the two mRNA vaccine series are detected in patient populations that have a high seronegative rate. Providers should be aware that a substantial subset of vaccinated blood cancer patients may be at high risk of breakthrough COVID-19 infections. Further studies are needed to assess the status of the immune system in seronegative patients and develop options for protecting this vulnerable population,” the investigators concluded.