ABSTRACT
Background. COVID-19 vaccines reduce the incidence of severe clinical outcomes, however, some patients remain at risk of severe disease. The primary aim of this large, nationwide retrospective cohort was to identify risk factors for severe disease despite vaccination. Methods. Nationwide cohort study of US Veteran patients with laboratoryconfirmed SARS-CoV-2 infection after vaccination. The primary outcome was development of severe COVID-19 disease, defined as a hospitalization within 14 days of a positive SARS-CoV-2 diagnostic test and either SpO2 <= 94%, receipt of supplemental oxygen, mechanical ventilation, or death within 28 days. Exposure variables included demographic and clinical risk factors, receipt of an additional vaccine dose, and calendar months since initial vaccination series. Data were analyzed using logistic regression, and adjusted odds ratios (aORs) are presented. Results. Among 111,151 breakthrough infections, 110,760 had disease severity assessments and were included. 14,690/110,790 (13.3%) were hospitalized with severe COVID-19 or died. Risk factors for severe disease are presented in Figure 1. The strongest risk factor for severe disease despite vaccination was age. Immunocompromising conditions, including immunosuppressive medications (Cytokine-blocking, aOR, 1.73, CI, 1.37-2.18;receipt of glucocorticoids, aOR, 2.41, CI, 2.25, 2.58;leukocyte inhibitory, aOR 2.44, CI, 1.98-2.99;lymphocyte-depleting, aOR, 2.12, 1.61-2.79), cytotoxic chemotherapy within 6 months (aOR, 2.69;CI, 2.25, 3.21), and leukemias/lymphomas were also associated with increased risk (aOR, 1.84, CI, 1.59-2.14), as were chronic conditions associated with end-organ disease. Receipt of an additional (booster) dose of vaccine was associated with reduced odds of severe disease, with risk reduction from vaccination and boosting strongest during the months immediately following vaccine doses. Variables with aOR <1 are associated with reduced odds of severe breakthrough infections and variables with aOR >1 are associated with increased odds of severe breakthrough infections. Referent groups for multicategory variables are listed in bold. Presented with a logarithmic scale. Conclusion. In this nationwide cohort, we identified risk factors for severe disease despite vaccination. Findings can be used to inform outreach efforts for booster vaccinations and to inform clinical decision making about risk and to identify patients who would benefit from interventions in addition to vaccination, such as preexposure prophylaxis and antiviral therapy. (Table Presented).
ABSTRACT
Introduction Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is particularly serious in patients with multiple myeloma (MM), with estimated mortality of over 30% in several studies. In the general population, SARS-CoV-2 vaccination has been demonstrated to be an effective approach to preventing infection. However, patients with MM were not included in vaccination trials. Recent studies suggest that patients with compromised immune systems exhibit reduced antibody response to SARS-CoV-2 vaccination, and MM patients are often immunocompromised both due to MM itself and due to MM treatment. Thus, the objective of this retrospective cohort study in the national Veterans Affairs (VA) healthcare system was to evaluate the real-world effectiveness of SARS-CoV-2 vaccination to prevent COVID-19 infection in MM patients during the 140-day period following initial vaccine availability. Methods This is a multicenter study of SARS-CoV-2 infection among vaccinated and unvaccinated patients at VA hospitals nationwide during the period from 12/15/2020 to 5/4/2021. We identified a cohort of MM patients who were alive and without prior SARS-CoV-2 infection on their date of vaccination or inclusion as a control. For added comparison with a less immunocompromised population, we also identified a cohort of cancer survivors, defined as patients with any solid or hematologic malignancy who had been treated with systemic cancerdirected therapy subsequent to 8/15/2010, but had not been treated with such therapy in the 6 months prior to vaccination or inclusion as a control, and were alive and without prior SARS-CoV-2 infection on that date. Vaccinated patients were exactly matched 1:1 to unvaccinated controls on race, VA facility, rurality of home address, cancer type, and treatment timing and modality with minimum distance matching on age. The primary exposure was receipt of a SARS-CoV-2 vaccine. The primary outcome was laboratory-confirmed SARS-CoV-2 infection. Vaccination effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared to unvaccinated controls. Results 6,891 MM patients met eligibility criteria and 4,367 were vaccinated during the study period. Of those, 1,606 vaccinated MM patients were matched 1:1 to 1,606 unvaccinated or not yet vaccinated controls. In addition, for comparison, 2,476 vaccinated cancer survivors were matched 1:1 to 2,476 unvaccinated or not yet vaccinated controls. Median follow-up was 44 days among MM patients and 46 days among cancer survivors. Vaccine effectiveness in the matched cohort of MM patients was 22.2% (95% CI, -133 to 82.7%) starting 14 days after the second dose. In contrast, effectiveness was 82.3% (95% CI 16.4 to 100%) starting 14 days after the second dose in the matched cohort of cancer survivors. Among vaccinated MM patients in the matched cohort, 14 (8.7 per 1000 patients) were infected with SARS-CoV-2 subsequent to vaccination. Among vaccinated cancer survivors in the matched cohort, 10 (4.0 per 1000 patients) were infected subsequent to vaccination. Conclusion Vaccination is an effective strategy for preventing SARS-CoV-2. However, effectiveness may be reduced in patients with MM, likely due to a co-existing immunosuppression both due to the disease process as well as associated therapy. Future studies are needed to evaluate the relationship between MM disease states, types of therapy used and treatment timing that may impact vaccine effectiveness, and to also determine if MM patients would benefit from post-vaccination serologies or a booster vaccination.
ABSTRACT
Background: Data is lacking about SARS-CoV-2 vaccination effectiveness in patients with cancer, particularly those on systemic therapy. This retrospective cohort study in the US national Veterans Affairs (VA) healthcare system reports the effectiveness of SARS-CoV-2 vaccination in cancer patients on and off active therapy during the first 140 days following administration. Methods: This is a multicenter study of SARS-CoV-2 infection among vaccinated and unvaccinated Veterans vaccinated during the period from 12/15/2020 to 5/4/2021. Veterans with solid or hematologic malignancy who received systemic cancer-directed therapy at the VA at least one time between 8/15/2010 to 5/4/2021 were included. Vaccinated patients were exactly matched 1:1 to an unvaccinated control on race, VA facility, rurality of home address, cancer type, and treatment timing and modality with minimum distance matching on age. The primary exposure was receipt of a SARS-CoV-2 vaccine. The primary outcome was laboratory-confirmed SARS-CoV-2 infection. Vaccination effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared to unvaccinated controls. Results: 184,485 patients met eligibility criteria and 113,796 were vaccinated during the study period. Of these, 29,152 vaccinated patients were matched 1:1 to 29,152 unvaccinated or not yet vaccinated controls. As of a median 47 days of follow-up, overall vaccine effectiveness in the matched cohort was 58% (95% CI, 39 to 72%) starting 14 days after the second dose. Patients on chemotherapy within three months prior to first vaccination dose exhibited a 14-day post-second dose effectiveness of 57% (95% CI -23 to 90%), versus 76% (95% CI 50 to 91%) for those on endocrine therapy and 85% (95% CI 29 to 100%) for those off systemic therapy for at least six months prior. Conclusions: Vaccination is an effective strategy for preventing COVID-19 in cancer patients. However, effectiveness may be reduced in patients actively receiving immunosuppressive systemic therapy. Future study is needed to determine if these patients would benefit from post-vaccination serologies and/or a booster vaccination following completion of therapy. Legal entity responsible for the study: Nathanael Fillmore. Funding: Has not received any funding. Disclosure: W. Branch-Elliman: Financial Interests, Institutional, Funding: Gilead. G. Parmigiani: Financial Interests, Personal, Leadership Role: Phaeno Biotechnology. M. Brophy: Financial Interests, Personal, Research Grant: Novartis. N. Munshi: Financial Interests, Personal, Advisory Role: Celgene;Financial Interests, Personal, Advisory Role: Janssen;Financial Interests, Personal, Advisory Role: AbbVie;Financial Interests, Personal, Advisory Role: Takeda;Financial Interests, Personal, Member of the Board of Directors: OncoPep. All other authors have declared no conflicts of interest.