Patterns of neutralizing humoral response to SARS-CoV-2 infection among hematologic malignancy patients reveal a robust immune response in anti-cancer therapy-naive patients (original) (raw)
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JAMA Oncology
IMPORTANCE To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer. OBJECTIVE To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination. MAIN OUTCOMES AND MEASURES Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively. RESULTS In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001). CONCLUSIONS AND RELEVANCE In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.
British Journal of Haematology, 2021
COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26Á2%) had myeloid, 121 (51Á1%) lymphoid and 54 (22Á8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3Á42; 95% confidence interval (CI), 1Á04-11Á21; P = 0Á04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0Á35; 95% CI: 0Á11-1Á13; P = 0Á08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.
Cancer research communications, 2022
This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with haematological malignancies, and persons without cancer. For all cohorts, virus-neutralising immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL-2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of haematological malignancy patients, for whom both cancer type and treatment schedule were associated with non-response. Thus, whereas most myelodysplastic syndrome patients were conspicuously good responders, some patients with other haematological malignancies receiving cancer therapies within two weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunological insights that can inform health policy for cancer patients. Statement of significance Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: 1) clarified in cancer patients the degree of waning of antibodies, serum neutralisation titres against parental virus and variants of concern, and T cell responses; 2) evaluated the immune response among cancer patients to a third dose of COVID-19 vaccine; and 3) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in cancer patients.
Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understandin...
This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity wa...
CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wild-type (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced...
Acta Medica Academica, 2023
Objective. Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies. Methods. Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer. Results. Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine. Conclusion. Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients.
Humoral Responses After SARS-CoV-2 mRNA Vaccination and Breakthrough Infection in Cancer Patients
Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 2021
Objective: To evaluate the magnitude of humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with cancer receiving active therapies. Patients and Methods: Patients 18 years or older in whom SARS-CoV-2 spike antibody (anti-S Ab) levels were measured after 2 doses of SARS-CoV-2 mRNA vaccines were included. Patients with prior coronavirus disease 2019 (COVID-19) infection or receiving other immunosuppressive therapy were excluded. Results: Among 201 patients who met the criteria, 61 were immunocompetent, 91 had a hematologic malignancy, and 49 had a solid malignancy while receiving treatments associated with cytopenia, including chemotherapy or cyclin-dependent kinase 4 and 6 inhibitors. A significantly greater proportion of immunocompetent patients (96.7% [59 of 61]) had anti-S Ab titers of 500 U/mL or greater compared to patients with hematologic (7.7% [7 of 91) and solid (55.1% [27 of 49]) malignancy (P<.001). Despite 2 doses of SARS-CoV-2 mRNA vaccines, 52.7% of patients with hematologic malignancy (48 of 91) and 8.2% of those with solid malignancy (4 of 49) receiving cytopenic therapy had no seroconversion (spike antibody titers <0.8 U/mL). Two patients subsequently had development of breakthrough COVID-19 infection after full vaccination. Conclusion: A substantial proportion of patients with hematologic and solid malignancies receiving chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. Our study adds to a growing body of literature suggesting that immunosuppressed patients have a suboptimal humoral response to COVID-19 vaccination. Our study also underscores the importance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.
Immune Response to SARS-CoV-2 Vaccination in Cancer Patients: A Prospective Study
Cureus
Introduction Cancer patients on active treatment are at increased risk of developing coronavirus disease 2019 (COVID-19), making effective immunization of the utmost importance. However, the effectiveness of vaccination in this population is still unclear. This study aims to evaluate the response against COVID-19 in a cohort of patients with active cancer under immunosuppressive therapy. Methods This was a prospective, cross-sectional, single-center study that included patients with cancer under immunosuppressive therapy vaccinated against COVID-19 between April and September 2021. Exclusion criteria were: previous known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, single-dose vaccine or incomplete vaccination scheme. Immunoglobulin G (IgG) anti-SARS-CoV-2 antibody levels were assessed using 35.2 binding antibody units (BAU)/mL as the positive cutoff. Assessments were performed 14-31 days after the first and second dose and three months after the second dose. Results A total of 103 patients were included. The median age was 60 years. Most patients were being treated for gastrointestinal cancer (n=38, 36.9%), breast cancer (n=33, 32%) or head and neck cancer (n=18, 17.5%). At evaluation, 72 patients (69.9%) were being treated with palliative intent. The majority were being treated with chemotherapy (CT) alone (57.3%). At the first assessment, levels of circulating SARS-CoV-2 IgG consistent with seroconversion were present in 49 patients (47.6%). At the time of the second assessment, 91% (n=100) achieved seroconversion. Three months after the second dose, 83% (n=70) maintained levels of circulating SARS-CoV-2 IgG consistent with seroconversion. In this study, no SARS-CoV-2 infection was reported in the study population. Conclusions Our findings suggest that this group of patients had a satisfactory COVID-19 immunization response. Although promising, this study should be replicated on a wider scale in order to validate these findings.