Immunogenicity of The BNT162b2 mRNA COVID-19 Vaccine in Patients With Primary Brain Tumors: A Prospective Cohort Study

Immunogenicity of The BNT162b2 mRNA COVID-19 Vaccine in Patients With Primary Brain Tumors: A Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Immunogenicity of The BNT162b2 mRNA COVID-19 Vaccine in Patients With Primary Brain Tumors: A Prospective Cohort Study Amir Massarweh, Roi Tschernichovsky, Amos Stemmer, Alexandra Benouaich-Amiel, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-986572/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jan, 2022 Read the published version in Journal of Neuro-Oncology → Version 1 posted 4 You are reading this latest preprint version Abstract Purpose Immunogenicity of Covid-19 vaccines may be negatively impacted by anti-cancer treatment. The management of primary brain tumor (PBT) patients routinely includes temozolomide and steroids, which are immune-suppressive. In this study, we aimed to determine the rate of seropositivity in PBT patients following receipt of two doses of the BNT162b2 vaccine. Methods We prospectively evaluated IgG antibody levels against SARS-CoV-2 spike protein in 17 PBT patients following two doses of the BNT162b2 mRNA vaccine. IgG levels were collected at two time points: T1 - after a median of 44 days from the second vaccine dose and T2 - after a median of 130 days from the second dose. Titers were compared against a group of healthy controls (HC) comprised of patients’ family members/caregivers. Results At T1, 88.2% (15/17) of PBT patients achieved seroconversion, compared with 100% (12/12) of HCs. Median IgG titer was significantly lower in the PBT group compared to the HC group (1,908 AU/mL vs 8,198 AU/mL, respectively; p=0.002). At T2, 80% (12/15) of PBT achieved seroconversion, compared to 100% (10/10) of the HCs. Median IgG titer remained significantly lower in the PBT group (410 vs 1687; p=0.002). All three PBT patients who failed to seroconvert at T2 had been treated with corticosteroids during vaccination. In a univariate analysis, steroid use was negatively associated with antibody titer. Conclusion Most PBT patients achieve seroconversion after receiving the BNT162b2 vaccine, but with lower IgG titer compared to HCs. Steroid use during the vaccination period is associated with lower titer. Neurology Oncology Glioma Covid-19 Vaccine mRNA BNT162b2 Figures Figure 1 Figure 2 Introduction More than 18 months after the first reported cases of Covid-19, the global community is still struggling to curb the pandemic. Vaccines for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at the heart of this effort, with more than 4 billion doses administered globally as of August 2021‎‎ 1 ,‎ 2 . At the time of the initial vaccine rollouts, there was scarce data regarding efficacy in the oncology space. Patients with cancer were under-represented in the original phase III trials leading up to the approval of the BNT126b2 (Pfizer), mRNA-1273 (Moderna) and Ad26.COV2.S (Janssen) vaccines, and efficacy was not analyzed separately for this patient subgroup ‎‎ 3 ,‎ 4 ,‎ 5 . More recently, there have been reports indicating that the immunogenicity of the mRNA vaccine is attenuated in cancer patients, most notably in patients with hematological cancer actively receiving treatment ‎ 6 ,‎ 7 ,‎ 8 ,‎ 9 ,‎ 10 ,‎ 11 . In solid cancer patients, seroconversion rates appear to lag behind those of healthy controls over the two-dose schedule, and are accompanied by consistently lower IgG antibody titers ‎ 11 ‎, 12 . Importantly, titers are differentially impacted by different anti-neoplastic treatment modalities ‎ 10 ‎, 11 . Given that immunogenicity seems to vary by anti-cancer treatment type, primary brain tumor patients and gliomas in particular are potentially at high risk for a sub-optimal response to vaccination. The treatment of glioma patients is multi-faceted and typically includes maximal surgical resection for operable patients, followed by post-operative radiation therapy. Temozolomide (TMZ) is administered in the adjuvant setting for low grade gliomas while concurrent and adjuvant temozolomide is routinely used in high grade tumors. Temozolomide, an alkylating agent, is known to cause hematological toxicity to a significant degree, including lymphopenia and neutropenia, which might hinder the humoral response to the vaccine ‎ ‎‎ 13 ‎, 14 ‎, 15 . Further contributing to immunosuppression in glioma patients is the frequent administration of glucocorticoids, commonly prescribed to reduce cerebral edema and alleviate the associated neurological symptoms‎ 16 . There is very limited data on the use of steroids and its impact on Covid-19 vaccine efficacy ‎‎ 17 ,‎ 18 . Still, under the caveat of limited data, the updated Center for Disease Control (CDC) guidelines single out receipt of prednisone in a dose greater than 20mg/day for more than 14 days as a putative risk factor for a reduced response to vaccination‎‎ 19 . So far, only a handful of primary brain tumor cases were included in the pan-cancer studies evaluating immunogenicity of Covid-19 vaccines in cancer patients ‎‎ 7 ,‎ 8 ,‎ 9 ,‎ 10 . Furthermore, brain tumor patients’ respective treatment modalities and their impact on seroconversion rates were not assessed. In this study, we aimed to shed further light on this pressing issue by using a brain tumor-only cohort of patients which have undergone a two-dose vaccination schedule with the BNT162b2 mRNA vaccine. Materials & Methods Study Population The study population comprises a nested cohort of consecutive primary brain tumor (PBT) patients, derived from a larger pan-cancer cohort recently reported on by our group ‎ 8 . The original cohort included adult patients (>18 years of age) with a histologically - confirmed diagnosis of solid malignancy, who were undergoing active anti-neoplastic treatment, had previously received 2 doses of the BNT162b2 mRNA Covid-19 vaccine, and were at least 30 days following the second (“boost”) vaccination dose at the time of accrual. Of 102 cancer patients in the original cohort, 9 patients were diagnosed with a primary brain tumor. In the present cohort, the subset of brain tumor patients was expanded to include a total of 17 cases. Treatment received by each patient were recorded at accrual (surgery, radiotherapy, temozolomide, bevacizumab, steroids, others). The healthy control (HC) group was assembled from each cancer patient’s respective family members/caregiver who accompanied him/her to the treatment center and had received 2 doses ofBNT162b2. Exclusion criteria for both groups included history of prior Covid-19 infection (based on a positive polymerase chain reaction [PCR] test), active hematological cancer and pregnancy. Additional exclusion criteria for the control group included immune deficiency, active receipt of immunosuppressant therapy of any kind, and active other malignancy of any kind. Determination of serological status Blood samples were extracted from all participants at two separate time points. The first sample (“T1”) was drawn at least 37 days after the second vaccine dose, between March 1st 2021 and June 10th 2021. The second sample (“T2”) was drawn at least two months after the first sample, between May 18th 2021 and July 22nd 2021. Serological status was determined using IgG antibodies level against the SARS-CoV-2 spike receptor-binding domain, quantified using a chemiluminescent microparticle immunoassay (by Abbott©). An antibody level of 50 AU/mL or higher was considered positive for successful seroconversion‎ 20 ‎. Statistical Analysis Univariate and multivariable analyses were performed by fitting a generalized linear model on the log of IgG values at T2 and included age and days after vaccination as continuous variables, and sex, treatments (except for the study drug), and steroid use at vaccination as categorical variables. The Spearman correlation method was used to assess the correlation between the IgG values and the number of days after vaccination. The difference in IgG values between patients and controls was evaluated using the Wilcoxon rank sum test. A P value <.05 was considered significant. Statistical analysis was performed using R, version 4.0.2 (R Foundation). Ethics Statement The study was approved by the Rabin Medical Center Ethics Committee and all patients as well as HC provided informed consent. Results Characteristics of study population A total of 17 PBT patients and 12 HCs were included in the study (see Table 1 ). The PBT group comprised 11 male patients, with a median age of 65 (58-71). In the HC group, 2 participants were male and the median age was 58 (48-69). Most patients in the PBT group had a glioma diagnosis (glioblastoma multiforme=13, anaplastic astrocytoma=2, oligodendroglioma=1). A single patient with a non-glioma diagnosis (atypical meningioma) was included based on having been treated with bevacizumab, a drug commonly prescribed for glioma in the second-line setting. Table 1 Study Population PBT (n=17) HC (n=12) Age (median [IQR]) 65 (58-71) 58 (48-69) Sex n (%) male 11 (65%) 2 (17%) Female 6 (35%) 10 (83%) Diagnosis n (%) Glioblastoma 13 (76%) n/a Anaplastic astrocytoma 2 (12%) n/a Oligodendroglioma 1 (6%) n/a Atypical meningioma 1 (6%) n/a Treatment components in the three months prior to vaccination Radiation 5(27%) n/a Temozolomide 11(65%) n/a Bevacizumab 4 (23%) n/a Clinical trial drug 1 (6%) n/a Surgery 2 (12%) n/a Corticosteroids at time of vaccination 8/17 (47%) n/a Corticosteroid (Dexamethasone) dosage (mean mg [range]) 0.5 (0-16) n/a IQR = Interquartile range Eleven patients received TMZ and four patients received bevacizumab within three months prior to vaccination. Eight patients were under systemic glucocorticoid treatment at the time of vaccination. Serological outcome At timepoint T1, the median elapsed time in days from the 2nd vaccination dose was 44 (37-53) for the PBT group and 44 (34 -51) for the HC group (p=0.8) [see Table 2 ]. At this timepoint, 88.2% (15/17) of PBT patients achieved seroconversion, compared with 100% (12/12) of HCs. Median IgG titer levels were significantly lower in the PBT group compared to the HC group (1,908 AU/mL vs 8,198 AU/mL, respectively; p=0.002) [see Table 2, Fig. 1 ] Table 2: Serological Status Brain Tumor Patients Control p-value Timepoint T1 Days post-vaccination (median [IQR]) 44 (37-53) 44 (34 -51) 0.8 Seroconversion Rate (%) 88.2% (15/17) 100% (12/12) IgG Titer Values (AU/mL) (median [IQR]) 1,908 (471 - 4,387) 8,198 (4,515 - 12,377) 0.002 Timepoint T2 Days post-vaccination (median [IQR]) 130 (126 -138) 134 (126 -140) >0.9 Seroconversion Rate (%) 80% (12/15) 100%(12/12) IgG Titer Values (AU/mL) (median [IQR]) 410 (138 - 770) 1,687 (937 - 2,326) 0.002 IQR: interquartile range At T2, the median elapsed time in days from 2nd vaccination was 130 (126-138) and 134 (126-140) for the PBT and HC groups, respectively. IgG levels were available for 10 out of 12 patients in the HC group, with a seroconversion rate of 100% (10/10). In the PBT group, IgG level were available for 15 out of 17 patients, with a seroconversion rate of 80% (12/15). Two PBT patients who were seronegative at T1 remained so at T2. One PBT patient who successfully seroconverted at T1 (IgG level of 189 AU/mL) reverted back to a negative status at T2 (IgG level of 42 AU/mL). Median IgG titers remained significantly lower in the PBT group (410 vs 1687; p=0.002) [see Fig. 1 ]. Analysis of IgG levels as a function of time elapsed from 2nd vaccination at T2 revealed significant inverse correlations for both groups (see Fig. 2 ). Steroid treatment at the time of vaccination Notably, all three PBT patients who failed to achieve seroconversion at T2 had been treated with corticosteroids at the time of vaccination, with two patients out of the three receiving high dose dexamethasone (10 mg and 16 mg, respectively). Of the PBT patients who successfully seroconverted at T2, four patients were under steroid treatment, however all four were treated with low doses (between 0.5 and 4 mg). Congruently, in a univariate analysis at timepoint T2, corticosteroid use was negatively associated with diminished IgG titers. The association was not significant in a multivariable analysis. Male sex was positively associated with IgG titers. No additional putative risk factors for diminished titers were identified (see Table 3 ). Table 3: Univariate & Multivariable Analysis at Timepoint T2 Univariate analysis Multivariate analysis Characteristic Beta 95% CI p-value Beta 95% CI p-value Age -0.03 -0.08, 0.03 0.3 0.01 -0.03, 0.05 0.6 Sex Female - - - - Male 1.5 0.22, 2.8 0.039 1.7 0.91, 2.5 0.014 Treatments Bevacizumab - - - - Surgery 1.6 -0.92, 4.1 0.2 1.0 -1.2, 3.2 0.4 Temozolomide -0.36 -2.2, 1.4 0.7 -0.2 -0.93, 0.54 0.6 Elapsed time from vaccination (days) -0.03 -0.06, 0.01 0.2 -0.01 -0.02, 0.01 0.5 Steroid treatment a t vaccination No - - - - Yes -1.9 -3.0, -0.82 0.005 -1.1 -1.9, -0.25 0.063 Diagnosis Anaplastic Astrocytoma - - - - Atypical Meningioma 0.22 -3.2, 3.7 >0.9 2.4 0.51, 4.2 0.066 Glioblastoma Multiforme -1.3 -3.4, 0.91 0.3 0.37 -1.1, 1.9 0.7 Oligodendroglioma 0.67 -2.8, 4.1 0.7 0.08 -1.4, 1.5 >0.9 Discussion To our knowledge, this is the largest reported cohort of PBT patients assessed for serological status following two doses of the BNT162b2 mRNA Covid-19 vaccine. Eighty percent of PBT patients in our study seroconverted followings a two-dose vaccination schedule, which is a lower rate than was previously recorded in pan-cancer cohorts, including from our group ‎ 11 ,‎ 12 . As with the previous pan-cancer cohorts, median IgG titers in the PBT group were significantly lower compared with HCs, and remained lower upwards of 4 months post-vaccination. The reduced immunogenicity observed in the PBT cohort should be interpreted with caution. First, while there is an agreed-upon laboratory IgG value above which a person is considered to have successfully seroconverted, the threshold required for actual real-life clinical protection against infection (a “protective threshold”) has not been established‎ 21 . In addition, whether or not lower IgG titers in seroconverted individuals necessarily confer greater risk of infection is also unclear. Early data does indicate, however, that breakthrough infections are correlated with lower peak levels of both neutralizing and S- specific IgG antibodies. This was recently demonstrated in a study from Israel conducted among vaccinated healthcare personnel‎ 22 . All three PBT patients who failed to successfully seroconvert at T2 were under daily corticosteroid treatment during the vaccination schedule, with two patients receiving high-dose dexamethasone. Indeed, a negative association between steroid treatment and IgG titers was confirmed in a univariate analysis. Interestingly, while four PBT patients who successfully seroconverted were also treated with steroids, none required dosing above 4 mg, suggesting that the level of impairment exerted by steroids on vaccine immunogenicity may be dose dependent. In contrast to our findings regarding steroids, there was no demonstrable association between receipt of TMZ in the peri-vaccination period and subsequent IgG titer levels. TMZ is known to induce lymphopenia which is driven primarily by selective CD4+ T-Cell Depletion‎ 15 ‎ , 23 . Therefore, any impairment to vaccine response exerted by TMZ would presumably be mediated through reduced CD4+ counts. In our study, longitudinal CD4 counts across the vaccination schedule were not routinely obtained, precluding a correlation analysis to be performed between CD4+ levels and humoral response. A relevant extrapolation could be made from the limited published data on vaccinated persons with HIV. Frater and colleagues recently reported safety and efficacy outcomes for a subset of 54 HIV-positive patients included in the phase II/III study of the ChAdOx1 nCoV-19 vaccine (Astra-Zeneca)‎‎‎ 24 . In the study, all participants were on active anti-retroviral therapy, had undetectable HIV viral load, and the median CD4 counts at enrollment were 694 cells/µL. The authors found no difference in the magnitude or durability of anti-spike IgG response between HIV-positive and HIV-negative participants, and there was no correlation between CD4 counts and the level of IgG response at day 56 following the prime vaccination (first dose). Our study suffers from several limitations. Primarily, small sample sizes in both groups prohibit making robust conclusions regarding vaccine immunogenicity in PBT patients. Secondly, the groups were not matched by age and sex – the proportion of males in the PBTs was higher, as was the median age. Lastly, cellular immunity measures - which are of relevance in patients receiving lymphocyte-modulating treatment, were not assessed. Notwithstanding the above limitations, our findings do point to a reduced vaccine response in PBT patients compared with healthy controls, as evidenced by a lower rate of successful seroconversion, as well as reduced IgG levels over a prolonged follow-up period. Both of these effects might be mediated by chronic steroid use throughout the vaccination schedule. In light of our findings, it appears prudent to minimize corticosteroid treatment for PBT patients during the peri-vaccination period to the lowest-possible dose required to control edema-related symptoms. In addition, PBT patients should be strongly considered for receipt of a third (“booster”) vaccination dose. Alternatively, IgG titer levels may be serially monitored following the two-dose schedule to single out the subset of PBTs patients who serve to benefit from a booster dose. Like many other facets of oncology care, the treatment of neuro-oncology patients has been severely disrupted by the pandemic‎ 25 . Minimizing infection risk should be a high priority especially in patients with high - grade glioma, who typically harbor multiple risk factors for severe infection including older age, continuous immunosuppression, and reduced mobility secondary to neurological damage. Declarations Funding: No funding source to declare Competing Interests : the authors declare that they have no financial or non-financial interests that are directly or indirectly related to the work submitted for publication. Authorship : Substantial contribution to conception and design: N.E.R., S.M.S., S.Y.K Acquisition of data: A.M., A.B.A, S.M.S, S.Y.K Analysis and interpretation of data: A.M., R.T., A.S., N.E.R., S.M.M., S.Y.K. Drafting of article: R.T., A.S., N.E.R, S.M.S., S.Y.K Critical revision of article: RT, S.M.S., S.Y.K Final approval of version to be published: N.E.R, S.M.S, S.Y.K, R.T. Manuscript body word count : 2,040 Data Availability Statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. References Holder J (2021) Tracking Coronavirus Vaccinations Around The World. The New York Times. https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html . 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Urgent considerations for the neuro-oncologic treatment of patients with gliomas during the COVID-19 pandemic. 2020;22(7):912–917. doi: 10.1093/neuonc/noaa090 Cite Share Download PDF Status: Published Journal Publication published 11 Jan, 2022 Read the published version in Journal of Neuro-Oncology → Version 1 posted Reviews received at journal 20 Oct, 2021 Reviewers invited by journal 20 Oct, 2021 Editor assigned by journal 20 Oct, 2021 First submitted to journal 17 Oct, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-986572","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":57914131,"identity":"0425320b-3db6-4329-9ee0-3f7f3c33d32b","order_by":0,"name":"Amir Massarweh","email":"","orcid":"","institution":"Davidoff Cancer Center, Rabin Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Amir","middleName":"","lastName":"Massarweh","suffix":""},{"id":57914132,"identity":"170f3f62-540f-414f-b4c6-194474de3684","order_by":1,"name":"Roi Tschernichovsky","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYJACZiCWAzEOPCBKPRtEizFYSwIpWhIbQByitJjPb3/4uaDiXvr8sMMPgbbYyek2ENAic4zHWHrGmeLcjbfTDIBako3NDhDQIsHGw8bM25aQu3F2AkjLgcRthLWwP2Pm/ZeQbjg7/QOxWhjMmHkbEhLkpXOItiXHWJrnWILhBumcggMJBsT4hfn4w888NQny8rPTN3/4UGEnR1ALHBiAVRoQqxwE5BtIUT0KRsEoGAUjCgAADvA+n79KVxQAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3539-1940","institution":"Rabin Medical Center Davidoff Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Roi","middleName":"","lastName":"Tschernichovsky","suffix":""},{"id":57914133,"identity":"bb736f45-ebfc-43d1-a699-005bd2e51dda","order_by":2,"name":"Amos Stemmer","email":"","orcid":"","institution":"Department of Oncology, Sheba Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Amos","middleName":"","lastName":"Stemmer","suffix":""},{"id":57914134,"identity":"a7d951fa-431c-43db-b915-224068a86130","order_by":3,"name":"Alexandra Benouaich-Amiel","email":"","orcid":"","institution":"Davidoff Cancer Center, Rabin Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Benouaich-Amiel","suffix":""},{"id":57914135,"identity":"bbf80c10-97a7-4bec-b68b-35cbfb777048","order_by":4,"name":"Tali Siegal","email":"","orcid":"","institution":"Davidoff Cancer Center, Rabin Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tali","middleName":"","lastName":"Siegal","suffix":""},{"id":57914136,"identity":"359ae49a-04e5-428e-93d6-9aa97548183c","order_by":5,"name":"Noa Eliakim-Raz","email":"","orcid":"","institution":"Beilinson Hospital, Rabin Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Noa","middleName":"","lastName":"Eliakim-Raz","suffix":""},{"id":57914137,"identity":"3feee5b1-da34-4fb5-bdce-4e02e0b11b5f","order_by":6,"name":"Salomon M. Stemmer","email":"","orcid":"","institution":"Davidoff Cancer Center, Rabin Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Salomon","middleName":"M.","lastName":"Stemmer","suffix":""},{"id":57914138,"identity":"dbfa0d61-2969-4646-9f57-ecd04460507d","order_by":7,"name":"Shlomit Yust-Katz","email":"","orcid":"","institution":"Davidoff Cancer Center, Rabin Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shlomit","middleName":"","lastName":"Yust-Katz","suffix":""}],"badges":[],"createdAt":"2021-10-17 15:50:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-986572/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-986572/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11060-021-03911-7","type":"published","date":"2022-01-12T00:43:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":14799679,"identity":"a78cb892-afda-4413-bc49-14842e3d4fe6","added_by":"auto","created_at":"2021-10-22 14:36:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28471,"visible":true,"origin":"","legend":"See image above for figure legend","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-986572/v1/db36bdb127f259205552abb3.png"},{"id":14799680,"identity":"aee4344d-56df-4539-a1fa-2705e0e114d3","added_by":"auto","created_at":"2021-10-22 14:36:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58444,"visible":true,"origin":"","legend":"See image above for figure legend","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-986572/v1/6118aad6e90c03cf0e7231dd.png"},{"id":17226975,"identity":"e461ad18-5497-4ff5-8df8-7b3951091904","added_by":"auto","created_at":"2022-01-12 00:43:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":508215,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-986572/v1/bb1c371f-f89a-4b0f-a9b0-ca18bc2ab5aa.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eImmunogenicity of The BNT162b2 mRNA COVID-19 Vaccine in Patients With Primary Brain Tumors: A Prospective Cohort Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMore than 18 months after the first reported cases of Covid-19, the global community is still struggling to curb the pandemic. Vaccines for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at the heart of this effort, with more than 4 billion doses administered globally as of August 2021\u0026lrm;\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAt the time of the initial vaccine rollouts, there was scarce data regarding efficacy in the oncology space. Patients with cancer were under-represented in the original phase III trials leading up to the approval of the BNT126b2 (Pfizer), mRNA-1273 (Moderna) and Ad26.COV2.S (Janssen) vaccines, and efficacy was not analyzed separately for this patient subgroup\u003csup\u003e\u0026lrm;\u0026lrm;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMore recently, there have been reports indicating that the immunogenicity of the mRNA vaccine is attenuated in cancer patients, most notably in patients with hematological cancer actively receiving treatment\u003csup\u003e\u0026lrm;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In solid cancer patients, seroconversion rates appear to lag behind those of healthy controls over the two-dose schedule, and are accompanied by consistently lower IgG antibody titers\u003csup\u003e\u0026lrm;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026lrm;,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Importantly, titers are differentially impacted by different anti-neoplastic treatment modalities \u003csup\u003e\u0026lrm;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026lrm;,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGiven that immunogenicity seems to vary by anti-cancer treatment type, primary brain tumor patients and gliomas in particular are potentially at high risk for a sub-optimal response to vaccination. The treatment of glioma patients is multi-faceted and typically includes maximal surgical resection for operable patients, followed by post-operative radiation therapy. Temozolomide (TMZ) is administered in the adjuvant setting for low grade gliomas while concurrent and adjuvant temozolomide is routinely used in high grade tumors. Temozolomide, an alkylating agent, is known to cause hematological toxicity to a significant degree, including lymphopenia and neutropenia, which might hinder the humoral response to the vaccine \u0026lrm;\u003csup\u003e\u0026lrm;\u0026lrm;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026lrm;,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026lrm;,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Further contributing to immunosuppression in glioma patients is the frequent administration of glucocorticoids, commonly prescribed to reduce cerebral edema and alleviate the associated neurological symptoms\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. There is very limited data on the use of steroids and its impact on Covid-19 vaccine efficacy\u003csup\u003e\u0026lrm;\u0026lrm;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Still, under the caveat of limited data, the updated Center for Disease Control (CDC) guidelines single out receipt of prednisone in a dose greater than 20mg/day for more than 14 days as a putative risk factor for a reduced response to vaccination\u0026lrm;\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSo far, only a handful of primary brain tumor cases were included in the pan-cancer studies evaluating immunogenicity of Covid-19 vaccines in cancer patients\u003csup\u003e\u0026lrm;\u0026lrm;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Furthermore, brain tumor patients\u0026rsquo; respective treatment modalities and their impact on seroconversion rates were not assessed. In this study, we aimed to shed further light on this pressing issue by using a brain tumor-only cohort of patients which have undergone a two-dose vaccination schedule with the BNT162b2 mRNA vaccine.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThe study population comprises a nested cohort of consecutive primary brain tumor (PBT) patients, derived from a larger pan-cancer cohort recently reported on by our group\u003csup\u003e\u0026lrm;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe original cohort included adult patients (\u0026gt;18 years of age) with a histologically - confirmed diagnosis of solid malignancy, who were undergoing active anti-neoplastic treatment, had previously received 2 doses of the BNT162b2 mRNA Covid-19 vaccine, and were at least 30 days following the second (\u0026ldquo;boost\u0026rdquo;) vaccination dose at the time of accrual. Of 102 cancer patients in the original cohort, 9 patients were diagnosed with a primary brain tumor. In the present cohort, the subset of brain tumor patients was expanded to include a total of 17 cases. Treatment received by each patient were recorded at accrual (surgery, radiotherapy, temozolomide, bevacizumab, steroids, others).\u003c/p\u003e \u003cp\u003eThe healthy control (HC) group was assembled from each cancer patient\u0026rsquo;s respective family members/caregiver who accompanied him/her to the treatment center and had received 2 doses ofBNT162b2. Exclusion criteria for both groups included history of prior Covid-19 infection (based on a positive polymerase chain reaction [PCR] test), active hematological cancer and pregnancy. Additional exclusion criteria for the control group included immune deficiency, active receipt of immunosuppressant therapy of any kind, and active other malignancy of any kind.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDetermination of serological status\u003c/h2\u003e \u003cp\u003eBlood samples were extracted from all participants at two separate time points. The first sample (\u0026ldquo;T1\u0026rdquo;) was drawn at least 37 days after the second vaccine dose, between March 1st 2021 and June 10th 2021. The second sample (\u0026ldquo;T2\u0026rdquo;) was drawn at least two months after the first sample, between May 18th 2021 and July 22nd 2021.\u003c/p\u003e \u003cp\u003eSerological status was determined using IgG antibodies level against the SARS-CoV-2 spike receptor-binding domain, quantified using a chemiluminescent microparticle immunoassay (by Abbott\u0026copy;). An antibody level of 50 AU/mL or higher was considered positive for successful seroconversion\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u0026lrm;.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eUnivariate and multivariable analyses were performed by fitting a generalized linear model on the log of IgG values at T2 and included age and days after vaccination as continuous variables, and sex, treatments (except for the study drug), and steroid use at vaccination as categorical variables. The Spearman correlation method was used to assess the correlation between the IgG values and the number of days after vaccination. The difference in IgG values between patients and controls was evaluated using the Wilcoxon rank sum test. A \u003cem\u003eP\u003c/em\u003e value \u0026lt;.05 was considered significant. Statistical analysis was performed using R, version 4.0.2 (R Foundation).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEthics Statement\u003c/h2\u003e \u003cp\u003e The study was approved by the Rabin Medical Center Ethics Committee and all patients as well as HC provided informed consent.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec8\"\u003e\n \u003ch2\u003eCharacteristics of study population\u003c/h2\u003e\n \u003cp\u003eA total of 17 PBT patients and 12 HCs were included in the study (see Table\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The PBT group comprised 11 male patients, with a median age of 65 (58-71). In the HC group, 2 participants were male and the median age was 58 (48-69). Most patients in the PBT group had a glioma diagnosis (glioblastoma multiforme=13, anaplastic astrocytoma=2, oligodendroglioma=1). A single patient with a non-glioma diagnosis (atypical meningioma) was included based on having been treated with bevacizumab, a drug commonly prescribed for glioma in the second-line setting.\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eStudy Population\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePBT (n=17)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHC (n=12)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (median [IQR])\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65 (58-71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58 (48-69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlioblastoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnaplastic astrocytoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOligodendroglioma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtypical meningioma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment components in the three months prior to vaccination\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRadiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTemozolomide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical trial drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCorticosteroids at time of vaccination\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/17 (47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCorticosteroid (Dexamethasone) dosage (mean mg [range])\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.5 (0-16)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003eIQR = Interquartile range\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eEleven patients received TMZ and four patients received bevacizumab within three months prior to vaccination. Eight patients were under systemic glucocorticoid treatment at the time of vaccination.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec9\"\u003e\n \u003ch2\u003eSerological outcome\u003c/h2\u003e\n \u003cp\u003eAt timepoint T1, the median elapsed time in days from the 2nd vaccination dose was 44 (37-53) for the PBT group and 44 (34 -51) for the HC group (p=0.8) [see \u003cstrong\u003eTable 2\u003c/strong\u003e]. At this timepoint, 88.2% (15/17) of PBT patients achieved seroconversion, compared with 100% (12/12) of HCs. Median IgG titer levels were significantly lower in the PBT group compared to the HC group (1,908 AU/mL vs 8,198 AU/mL, respectively; p=0.002) [see \u003cstrong\u003eTable 2, Fig.\u0026nbsp;1\u003c/strong\u003e]\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2: Serological Status\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBrain Tumor Patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTimepoint T1\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays post-vaccination\u0026nbsp;\u003c/strong\u003e(median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e44 (37-53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e44 (34 -51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeroconversion Rate\u0026nbsp;\u003c/strong\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e88.2% (15/17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e100% (12/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgG Titer Values (AU/mL)\u0026nbsp;\u003c/strong\u003e(median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e1,908 (471 - 4,387)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e8,198 (4,515 - 12,377)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTimepoint T2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays post-vaccination\u0026nbsp;\u003c/strong\u003e(median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e130 (126 -138)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e134 (126 -140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeroconversion Rate\u0026nbsp;\u003c/strong\u003e(%)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e80% (12/15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e100%(12/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.482384823848236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgG Titer Values (AU/mL)\u0026nbsp;\u003c/strong\u003e(median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.035230352303522%\"\u003e\n \u003cp\u003e410 (138 - 770)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.18428184281843%\"\u003e\n \u003cp\u003e1,687 (937 - 2,326)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.29810298102981%\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eIQR: interquartile range\u003c/p\u003e\n \u003cp\u003eAt T2, the median elapsed time in days from 2nd vaccination was 130 (126-138) and 134 (126-140) for the PBT and HC groups, respectively. IgG levels were available for 10 out of 12 patients in the HC group, with a seroconversion rate of 100% (10/10). In the PBT group, IgG level were available for 15 out of 17 patients, with a seroconversion rate of 80% (12/15). Two PBT patients who were seronegative at T1 remained so at T2. One PBT patient who successfully seroconverted at T1 (IgG level of 189 AU/mL) reverted back to a negative status at T2 (IgG level of 42 AU/mL). Median IgG titers remained significantly lower in the PBT group (410 vs 1687; p=0.002) [see \u003cstrong\u003eFig.\u0026nbsp;1\u003c/strong\u003e].\u003c/p\u003e\n \u003cp\u003eAnalysis of IgG levels as a function of time elapsed from 2nd vaccination at T2 revealed significant inverse correlations for both groups (see \u003cstrong\u003eFig.\u0026nbsp;2\u003c/strong\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec10\"\u003e\n \u003ch2\u003eSteroid treatment at the time of vaccination\u003c/h2\u003e\n \u003cp\u003eNotably, all three PBT patients who failed to achieve seroconversion at T2 had been treated with corticosteroids at the time of vaccination, with two patients out of the three receiving high dose dexamethasone (10 mg and 16 mg, respectively). Of the PBT patients who successfully seroconverted at T2, four patients were under steroid treatment, however all four were treated with low doses (between 0.5 and 4 mg).\u003c/p\u003e\n \u003cp\u003eCongruently, in a univariate analysis at timepoint T2, corticosteroid use was negatively associated with diminished IgG titers. The association was not significant in a multivariable analysis. Male sex was positively associated with IgG titers. No additional putative risk factors for diminished titers were identified (see Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3: Univariate \u0026amp; Multivariable Analysis at Timepoint T2\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.833333333333332%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"33.666666666666664%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"37.5%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e-0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-0.08, 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-0.03, 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e0.22, 2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e0.91, 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatments\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Bevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-0.92, 4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-1.2, 3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Temozolomide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e-0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-2.2, 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e-0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-0.93, 0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u003cstrong\u003eElapsed time from\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evaccination\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e-0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-0.06, 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e-0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-0.02, 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSteroid treatment a\u003c/strong\u003e\u003cstrong\u003et\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evaccination\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e-1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-3.0, -0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e-1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-1.9, -0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003eAnaplastic Astrocytoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003eAtypical\u0026nbsp;Meningioma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-3.2, 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e0.51, 4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003eGlioblastoma Multiforme\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e-1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-3.4, 0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-1.1, 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.881469115191987%\"\u003e\n \u003cp\u003eOligodendroglioma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.514190317195325%\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.524207011686144%\"\u003e\n \u003cp\u003e-2.8, 4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.186978297161936%\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.023372287145243%\"\u003e\n \u003cp\u003e-1.4, 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.185308848080133%\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the largest reported cohort of PBT patients assessed for serological status following two doses of the BNT162b2 mRNA Covid-19 vaccine. Eighty percent of PBT patients in our study seroconverted followings a two-dose vaccination schedule, which is a lower rate than was previously recorded in pan-cancer cohorts, including from our group \u003csup\u003e\u0026lrm;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u0026lrm;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. As with the previous pan-cancer cohorts, median IgG titers in the PBT group were significantly lower compared with HCs, and remained lower upwards of 4 months post-vaccination.\u003c/p\u003e \u003cp\u003eThe reduced immunogenicity observed in the PBT cohort should be interpreted with caution. First, while there is an agreed-upon laboratory IgG value above which a person is considered to have successfully seroconverted, the threshold required for actual real-life clinical protection against infection (a \u0026ldquo;protective threshold\u0026rdquo;) has not been established\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. In addition, whether or not lower IgG titers in seroconverted individuals necessarily confer greater risk of infection is also unclear. Early data does indicate, however, that breakthrough infections are correlated with lower peak levels of both neutralizing and S- specific IgG antibodies. This was recently demonstrated in a study from Israel conducted among vaccinated healthcare personnel\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAll three PBT patients who failed to successfully seroconvert at T2 were under daily corticosteroid treatment during the vaccination schedule, with two patients receiving high-dose dexamethasone. Indeed, a negative association between steroid treatment and IgG titers was confirmed in a univariate analysis. Interestingly, while four PBT patients who successfully seroconverted were also treated with steroids, none required dosing above 4 mg, suggesting that the level of impairment exerted by steroids on vaccine immunogenicity may be dose dependent.\u003c/p\u003e \u003cp\u003eIn contrast to our findings regarding steroids, there was no demonstrable association between receipt of TMZ in the peri-vaccination period and subsequent IgG titer levels. TMZ is known to induce lymphopenia which is driven primarily by selective CD4+ T-Cell Depletion\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u0026lrm;\u003csup\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Therefore, any impairment to vaccine response exerted by TMZ would presumably be mediated through reduced CD4+ counts. In our study, longitudinal CD4 counts across the vaccination schedule were not routinely obtained, precluding a correlation analysis to be performed between CD4+ levels and humoral response. A relevant extrapolation could be made from the limited published data on vaccinated persons with HIV. Frater and colleagues recently reported safety and efficacy outcomes for a subset of 54 HIV-positive patients included in the phase II/III study of the ChAdOx1 nCoV-19 vaccine (Astra-Zeneca)\u0026lrm;\u0026lrm;\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. In the study, all participants were on active anti-retroviral therapy, had undetectable HIV viral load, and the median CD4 counts at enrollment were 694 cells/\u0026micro;L. The authors found no difference in the magnitude or durability of anti-spike IgG response between HIV-positive and HIV-negative participants, and there was no correlation between CD4 counts and the level of IgG response at day 56 following the prime vaccination (first dose).\u003c/p\u003e \u003cp\u003eOur study suffers from several limitations. Primarily, small sample sizes in both groups prohibit making robust conclusions regarding vaccine immunogenicity in PBT patients. Secondly, the groups were not matched by age and sex \u0026ndash; the proportion of males in the PBTs was higher, as was the median age. Lastly, cellular immunity measures - which are of relevance in patients receiving lymphocyte-modulating treatment, were not assessed.\u003c/p\u003e \u003cp\u003eNotwithstanding the above limitations, our findings do point to a reduced vaccine response in PBT patients compared with healthy controls, as evidenced by a lower rate of successful seroconversion, as well as reduced IgG levels over a prolonged follow-up period. Both of these effects might be mediated by chronic steroid use throughout the vaccination schedule. In light of our findings, it appears prudent to minimize corticosteroid treatment for PBT patients during the peri-vaccination period to the lowest-possible dose required to control edema-related symptoms. In addition, PBT patients should be strongly considered for receipt of a third (\u0026ldquo;booster\u0026rdquo;) vaccination dose. Alternatively, IgG titer levels may be serially monitored following the two-dose schedule to single out the subset of PBTs patients who serve to benefit from a booster dose.\u003c/p\u003e \u003cp\u003eLike many other facets of oncology care, the treatment of neuro-oncology patients has been severely disrupted by the pandemic\u0026lrm;\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Minimizing infection risk should be a high priority especially in patients with high - grade glioma, who typically harbor multiple risk factors for severe infection including older age, continuous immunosuppression, and reduced mobility secondary to neurological damage.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding: \u0026nbsp;\u0026nbsp;\u003c/strong\u003eNo funding source to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e the authors declare that they have no\u0026nbsp;financial or non-financial interests that are directly or indirectly related to the work submitted for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSubstantial contribution to conception and design: N.E.R., S.M.S., S.Y.K \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcquisition of data: A.M., A.B.A, S.M.S, S.Y.K \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnalysis and interpretation of data: A.M., R.T., A.S., N.E.R., S.M.M., S.Y.K.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDrafting of article: R.T., A.S., N.E.R, S.M.S., S.Y.K\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCritical revision of article: RT, S.M.S., S.Y.K\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFinal approval of version to be published: N.E.R, S.M.S, S.Y.K, R.T.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eManuscript body word count\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e2,040\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHolder J (2021) Tracking Coronavirus Vaccinations Around The World. The New York Times. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html\u003c/span\u003e\u003c/span\u003e. Published January 29, Accessed August 6, 2021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLopez Bernal J, Andrews N, Gower C et al (2021) Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2108891\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePolack FP, Thomas SJ, Kitchin N et al (2020) Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. 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Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. 2021;137(23):3165\u0026ndash;3173. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood.2021011568\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonin L, Laing AG, Mu\u0026ntilde;oz-Ruiz M et al (2021) Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study. The Lancet Oncology 22(6):765\u0026ndash;778. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1470-2045(21)00213-8\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMassarweh A, Eliakim-Raz N, Stemmer A et al (2021) Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer. JAMA Oncol. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2021.2155\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalich R, Veyri M, Vozy A et al (2021) High seroconversion rate but low antibody titers after two injections of BNT162b2 (Pfizer-BioNTech) vaccine in patients treated with chemotherapy for solid cancers. Ann Oncol. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.annonc.2021.06.018\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAddeo A, Shah PK, Bordry N et al (2021) Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer. Cancer Cell. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ccell.2021.06.009\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEliakim-Raz N, Massarweh A, Stemmer A, Stemmer SM (2021) Durability of Response to SARS-CoV-2 BNT162b2 Vaccination in Patients on Active Anticancer Treatment. JAMA Oncol. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2021.4390\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoshen-Lago T, Waldhorn I, Holland R et al (2021) Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer. 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The Lancet HIV 8(8):e474\u0026ndash;e485. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S2352-3018(21)00103-X\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohile NA, Blakeley JO, Gatson NTN et al. Urgent considerations for the neuro-oncologic treatment of patients with gliomas during the COVID-19 pandemic. 2020;22(7):912\u0026ndash;917. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/neuonc/noaa090\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Glioma, Covid-19, Vaccine, mRNA, BNT162b2 ","lastPublishedDoi":"10.21203/rs.3.rs-986572/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-986572/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eImmunogenicity of Covid-19 vaccines may be negatively impacted by anti-cancer treatment. The management of primary brain tumor (PBT) patients routinely includes temozolomide and steroids, which are immune-suppressive. In this study, we aimed to determine the rate of seropositivity in PBT patients following receipt of two doses of the BNT162b2 vaccine.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe prospectively evaluated IgG antibody levels against SARS-CoV-2 spike protein in 17 PBT patients following two doses of the BNT162b2 mRNA vaccine. IgG levels were collected at two time points: T1 - after a median of 44 days from the second vaccine dose and T2 - after a median of 130 days from the second dose. Titers were compared against a group of healthy controls (HC) comprised of patients\u0026rsquo; family members/caregivers.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAt T1, 88.2% (15/17) of PBT patients achieved seroconversion, compared with 100% (12/12) of HCs. Median IgG titer was significantly lower in the PBT group compared to the HC group (1,908 AU/mL vs 8,198 AU/mL, respectively; p=0.002). At T2, 80% (12/15) of PBT achieved seroconversion, compared to 100% (10/10) of the HCs. Median IgG titer remained significantly lower in the PBT group (410 vs 1687; p=0.002). All three PBT patients who failed to seroconvert at T2 had been treated with corticosteroids during vaccination. In a univariate analysis, steroid use was negatively associated with antibody titer.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMost PBT patients achieve seroconversion after receiving the BNT162b2 vaccine, but with lower IgG titer compared to HCs. Steroid use during the vaccination period is associated with lower titer.\u003c/p\u003e","manuscriptTitle":"Immunogenicity of The BNT162b2 mRNA COVID-19 Vaccine in Patients With Primary Brain Tumors: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-22 14:36:07","doi":"10.21203/rs.3.rs-986572/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2021-10-21T01:05:02+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-10-20T12:59:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-10-20T06:58:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neuro-Oncology","date":"2021-10-17T11:50:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a4ce9dcd-089f-45cb-9ec9-7261b69cdba0","owner":[],"postedDate":"October 22nd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":8032336,"name":"Neurology"},{"id":8032337,"name":"Oncology"}],"tags":[],"updatedAt":"2022-01-12T00:43:26+00:00","versionOfRecord":{"articleIdentity":"rs-986572","link":"https://doi.org/10.1007/s11060-021-03911-7","journal":{"identity":"journal-of-neuro-oncology","isVorOnly":false,"title":"Journal of Neuro-Oncology"},"publishedOn":"2022-01-12 00:43:26","publishedOnDateReadable":"January 12th, 2022"},"versionCreatedAt":"2021-10-22 14:36:07","video":"","vorDoi":"10.1007/s11060-021-03911-7","vorDoiUrl":"https://doi.org/10.1007/s11060-021-03911-7","workflowStages":[]},"version":"v1","identity":"rs-986572","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-986572","identity":"rs-986572","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}