Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients

Zeng, Cong; Evans, John P.; Reisinger, Sarah A.; Woyach, Jennifer A.; Liscynesky, Christina; Boghdadly, Zeinab El; Rubinstein, Mark P.; Chakravarthy, Karthik; Saif, Linda J.; Oltz, Eugene M.; Gumina, Richard J.; Shields, Peter G.; Li, Zihai; Liu, Shan-Lu

doi:10.1186/s13578-021-00713-2

Cited by 37 publications

(49 citation statements)

References 12 publications

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“…This corroborated our previous findings in hematological cancer patients on similar B-cell depleting therapies. [ 17 ] Other studies have shown similar correlations between vaccine induced antibody levels and the time since last dose of anti-CD20 therapy. [ 18 ] Consistent with these observations, circulating CD20 cell levels also correlate with vaccine-induced antibody responses.…”

Section: Discussionmentioning

confidence: 80%

Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis

Gyang

Evans

Miller

et al. 2022

Multiple Sclerosis Journal - Experimental, Translational and Cl

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Background Patients with multiple sclerosis (pwMS) are often treated with disease modifying therapies (DMT) with immunomodulatory effects. This is of particular concern following the development of several vaccines to combat coronavirus disease 19 (COVD-19), a potentially fatal illness caused by SARS-CoV-2. Objectives To determine the efficacy of SARS-CoV-2 vaccination in pwMS and the impact of disease modifying therapies (DMT) on vaccine response. Methods This is a prospective longitudinal study in pwMS. Longitudinal serum samples were obtained prior to, and after SARS-CoV-2 mRNA vaccination. A novel neutralizing antibody (nAb) assay was used to determine nAbs titres against SARS-CoV-2 spike. Results We observed that (1) pwMS on B-cell depleting therapies exhibited reduced response to vaccination compared to other pwMS, correlating with time from last anti-CD20 infusion, (2) prior COVID-19 illness, DMT category, and pyramidal function were significant predictors of vaccine responsiveness, and (3) circulating absolute lymphocyte count (ALC) and IgG levels correlated with nAb levels. Conclusions We demonstrate that pwMS exhibit reduced nAb response to mRNA vaccination dependent on DMT status and identify predictive biomarkers for vaccine efficacy. We conclude that additional vaccination strategies may be necessary to achieve protective immunity in pwMS.

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Section: Discussionmentioning

confidence: 80%

Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis

Gyang

Evans

Miller

et al. 2022

Multiple Sclerosis Journal - Experimental, Translational and Cl

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“…However, the ability of mRNA-based SARS-CoV-2 vaccines to immunize primary or treatment-induced immunocompromised individuals has recently been questioned (Collier et al, 2021). In particular, patients with inflammatory bowel disease under infliximab treatment (Kennedy et al, 2021), patients who have received an allogeneic stem cell transplantation (Lafarge et al, 2022), cancer patients (Chung et al, 2021;Ribas et al, 2021;Zeng et al, 2021;Greenberger et al, 2021aGreenberger et al, , 2021bThakkar et al, 2021aThakkar et al, , 2021b, methotrexate treatment (Mahil et al, 2021), kidney transplant or hemodialysis (Bachelet et al, 2021;Danthu et al, 2021), or multiple sclerosis (Apostolidis et al, 2021) have all demonstrated a reduced ability to mount an immune response, potentially adversely affecting protection offered by vaccines. However, studies in which a comprehensive comparative analysis of both humoral and cellular immune responses after a third dose of vaccine is lacking.…”

Section: Introductionmentioning

confidence: 99%

mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients

et al. 2022

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SARS-CoV-2 vaccination has proven effective in inducing an immune response in healthy individuals and is progressively us allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-γ T-cell response in 328 subjects, including 131 immunocompromised individuals (cancer, rheumatologic, and hemodialysis patients), 160 health-care workers (HCW) and 37 subjects older than 75 yr, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that immunocompromised patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated immunocompromised individuals demonstrate a stronger SARS-CoV-2–specific immune response than those who are vaccinated without prior infection.

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“…Nevertheless, the immunocompromised state of patients with leukemia, a combination of disease and immunosuppressive therapies, has raised questions regarding the effectiveness of COVID-19 vaccines among people with leukemia [ 6 , 29 – 31 ]. Some of the strongest evidence regarding reduced antibody formation from COVID-19 relate to B-cell-depleting therapies, such as anti-CD20 monoclonal antibodies (e.g., rituximab, ofatumumab, obinutuzumab) [ 29 , 32 , 33 ]. Specifically, Zeng et al, using a study population comprised of patients with cancer and non-cancer control health care workers (HCW), demonstrated CLL demonstrated a lower mean antibody response than solid tumors and HCW controls; in comparing patients with CLL who were not prescribed B-cell-depleting therapy, B-cell-depleting therapy use was associated with lower mean antibody levels [ 32 ].…”

Section: Prevention and Management Of Covid-19 In Leukemia Patientsmentioning

confidence: 99%

How the COVID-19 Pandemic Reshaped the Management of Leukemia and Affected Patient Outcomes

Sharafeldin

Bates

Vachhani

2022

Curr. Treat. Options in Oncol.

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Opinion statement The coronavirus disease-19 (COVID-19) pandemic has posed numerous challenges to the global healthcare system. Of particular gravity is adult and pediatric patients with hematologic malignancies who are among the most vulnerable groups of patients at risk of severe COVID-19 outcomes. In the early phases of the pandemic, several treatment modifications were proposed for patients with leukemia. Largely speaking, these were adopting less-intense therapies and more utilization of the outpatient setting. Over time, our understanding and management have become more nuanced. Furthermore, equipped with vaccinations to prevent COVID-19 infection and availability of treatments in the presence of COVID-19 infection, the recommendations on management of patients with leukemia have evolved. Patient’s leukemia characteristics, possibility of targeted therapy, vaccination status, symptomatology, comorbidities, goal of anti-leukemic therapy, the intensity of therapy, the setting of treatment, as well as loco regional factors like dynamic incidence of COVID-19 in the community and hospital/ICU bed status are among many factors that influence the decisions. Furthermore, the oncology community has adopted delaying the anti-leukemia therapy for a limited time frame, if clinically possible, so as to still deliver most appropriate therapy while minimizing risks. Early adoption of growth factor support and conservative blood transfusion practices have helped as well. In this review, we discuss the impact of COVID-19 on outcomes and share considerations for treatments of leukemias. We describe the impact on both clinical care (from diagnosis to treatment) and research, and cover the literature on vaccines and treatments for COVID-19 in relation to leukemia.

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Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients

Cited by 37 publications

References 12 publications

Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis

Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis

mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients

How the COVID-19 Pandemic Reshaped the Management of Leukemia and Affected Patient Outcomes

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