key: cord-1004515-p5ifp1z3
authors: Becerril-Gaitan, Andrea; Vaca-Cartagena, Bryan F.; Ferrigno, Ana S.; Mesa-Chavez, Fernanda; Barrientos-Gutiérrez, Tonatiuh; Tagliamento, Marco; Lambertini, Matteo; Villarreal-Garza, Cynthia
title: Immunogenicity and Risk of SARS-CoV-2 Infection after COVID-19 Vaccination in Patients with Cancer: A Systematic Review and Meta-Analysis
date: 2021-10-26
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2021.10.014
sha: 44855aeba22778542a54ff4bc8e497db34296bf8
doc_id: 1004515
cord_uid: p5ifp1z3

BACKGROUND: Cancer patients are considered a priority group for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination given their high risk of contracting severe coronavirus disease 2019 (COVID-19). However, limited data exists regarding the efficacy of immunization in this population. In this study we assess the immunologic response after COVID-19 vaccination of cancer versus non-cancer population. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from March 01, 2020, through August 12, 2021. Primary endpoints were anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) seroconversion rates, T-cell response, and documented SARS-CoV-2 infection after COVID-19 immunization. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Overall effects were pooled using random effects models. RESULTS: This systematic review and meta-analysis included 35 original studies. Overall, 51% (95% confidence interval [CI], 41-62) and 73% (95%CI, 64-81) of cancer patients developed anti-S IgG above the threshold level after partial and complete immunization, respectively. Patients with hematologic malignancies had a significantly lower seroconversion rate than those with solid tumors after complete immunization (65% vs 94%; P<0.0001). Compared to non-cancer controls, oncological patients were less likely to attain seroconversion after incomplete (RR 0.45 [95%CI 0.35-0.58]) and complete (RR 0.69 [95%CI 0.56-0.84]) COVID-19 immunization schemes. Cancer patients had a higher likelihood of having a documented SARS-CoV-2 infection after partial (RR 3.21; 95%CI 0.35-29.04) and complete (RR 2.04; 95%CI 0.38-11.10) immunization. CONCLUSIONS: Cancer patients have an impaired immune response to COVID-19 vaccination compared to controls. Strategies that endorse the completion of vaccination schemes are warranted. Future studies should aim to evaluate different approaches that enhance oncological patients’ immune response.

Organization on March 11, 2020 , the world has faced an unprecedented socioeconomic and health crisis.

By September 24, 2021 , confirmed COVID-19 cases surpassed 230 million, and over 4.7 million deaths have been reported worldwide. [1] Cancer patients are a vulnerable group at increased risk of infection and COVID-19-related morbidity and mortality compared to the non-cancer population. [2, 3] A 30-day mortality rate of 20-25% has been documented in this group, [4] which is substantially higher than the estimated 3-4% among the general population. [5] Although several therapies in the general population such as dexamethasone, azithromycin, convalescent plasma, antivirals, Janus kinase 1/2 inhibitor, and monoclonal antibodies have been explored in the Randomized Evaluation of COVID-19 Therapy "RECOVERY" and COV-BARRIER studies, the vast majority did not show a decrease in mortality rate or length of hospitalization. [6, 7] A substantial proportion of hospitalized patients died even when receiving one of the few treatments that have shown an improvement in overall survival rate (i.e., dexamethasone, tocilizumab, baricitinib). [6, 8, 9] Thus, the development and widespread application of COVID-19 vaccines represents the most effective strategy for overcoming the current crisis. [10] Because cancer itself is an independent risk factor for poor prognosis, [11] international organizations such as the National Comprehensive Cancer Network (NCCN), the Asian Oncology Society, and the European Society for Medical Oncology have urged the prioritization of oncological patients for COVID-19 immunization. [12] [13] [14] Even though robust data confirms the safety and efficacy of SARS-CoV-2 vaccines' in preventing COVID-19 among the general population, [15, 16] data about their performance in oncological patients remain scarce. Recent studies reporting on COVID-19 immunogenicity using anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) titers, a surrogate of humoral response that has been correlated with neutralizing antibodies, [3, 17] have shown a sub-optimal response after immunization in cancer patients. [18] [19] [20] However, due to the exclusion and underrepresentation of cancer patients in most COVID-19 vaccines' clinical trials, [21] several gaps in knowledge persist regarding vaccines' J o u r n a l P r e -p r o o f effectiveness, best timing for administration, extent and durability of the attained immune response, and safety profile in this high-risk population. [21] To refine the existing evidence, a systematic review and meta-analysis was performed to assess seroconversion rates based on anti-S IgG titers following partial and complete COVID-19 immunization among oncological patients compared to non-cancer participants.

This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. [22] The complete protocol is available at the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42021261974) website. [23] Search strategy and selection criteria Studies needed to satisfy the following inclusion criteria: (1) assess immune humoral response rate in cancer patients based on anti-S SARS-CoV-2 IgG; (2) report original findings, (3) be in English, Spanish, or French language.

The following variables were recorded: first author; year of publication; study design and methodology; participants' median/mean age; number of controls and cancer patients; type of malignancy (i.e., solid vs hematological); proportion of cancer patients undergoing active treatment; type and number of COVID-19 vaccine doses administered; type of anti-S IgG immunoassay and threshold value used to define "vaccine responders"; proportion of cancer and non-cancer participants classified as "vaccine J o u r n a l P r e -p r o o f responders" and "vaccine non-responders" and their mean/median IgG titers; participants' T-cell response; and number of documented COVID-19 cases after vaccination. Two reviewers extracted the data in duplicate and disagreements were solved by a third author. For studies with ≥1 publication or having a superimposable population, only the largest study was included in the quantitative analysis.

To assess the risk of bias, 2 reviewers independently assessed the methodological quality of each study using the Risk of Bias in Non-randomized Studiesof Interventions (ROBINS-I) tool.

Disagreements among reviewers were solved by consensus.

The primary aim was to assess the proportion of oncological patients classified as vaccine responders, defined as the number of patients with anti-S SARS-CoV-2 IgG levels above each individual study's threshold value vs controls. We hypothesized that patients with hematological malignancies and those with partial immunization regimens would achieve inferior immunogenicity after COVID-19 immunization, thus, subgroup analyses assessing seroconversion rates between patients with solid vs hematologic malignancies, as well as partial and complete COVID-19 vaccination regimens, were conducted. As secondary outcomes, the proportion of documented SARS-CoV-2 infection and T-cell response after COVID-19 immunization in oncological and control subjects was assessed.

The proportion of oncological patients that achieved seroconversion and detectable T-cell response, as well as the percentage of patients diagnosed with SARS-CoV-2 infection after receiving at least one COVID-19 vaccine were assessed using generalized linear mixed-effects models of the logit-transformed proportions of individual studies. Confidence intervals (CI) of individual studies were calculated with the Clopper-Pearson method, while the Hartung-Knapp adjustment was employed to calculate the CI around the pooled effect. Between-study variability (τ 2 ) was estimated by the restricted maximum likelihood.

The effect size for binary outcomes is presented as risk ratios (RR) calculated with the Mantel-Haenszel method, with a corresponding 95%CI as forest plots. The method by Hartung-Knapp was used to adjust test statistics and 95%CI. The corresponding prediction intervals are also reported. Betweenstudy variance was estimated using the Paule-Mandel estimator for τ 2 , and heterogeneity between studies was assessed using the Higgins's I 2 and Cochran's Q tests. The relationship between effect estimates and study precision was assessed visually using funnel plots and the Harbord score test. In case asymmetry was detected, a limit meta-analysis was conducted to adjust for small-study effects.

Bivariate meta-regressions were used to assess type of COVID-19 vaccine (mRNA vs mRNA/viral vector), immunization scheme (incomplete vs complete), and time from last vaccine dose to serologic test (<3 vs ≥3 weeks from last dose) as explanatory variables, in terms of the studies' effect size (outcome variable) when determining the pooled RR of seroconversion rates. Sensitivity analyses were conducted to assess studies evaluating only mRNA vaccines, as well as for studies with low-to-moderate risk of bias. All statistical analyses were conducted using R statistical software (version 4.1.0, R Project for Statistical Computing) and RStudio software (version 1.4.1717, R Foundation for Statistical Computing ©). A 2-tailed P-value of <0.05 was considered significant.

The systematic literature search yielded 1,821 records, of which 1,287 remained after duplicates were excluded. Following title and abstract review, 1,233 records were excluded given that they reported nonoriginal findings, did not include cancer patients, or did not assess COVID-19 vaccines' immunogenicity.

Of the 54 articles that underwent full-text review, 35 articles [17] [18] [19] [20] were considered eligible and were included in the meta-analysis (Figure 1) . included both regimens. Only 18 studies had a control group (non-cancer patients). Table 1 summarizes the characteristics of the studies included in the meta-analysis. Most studies had a moderate risk of bias (Supplemental eTable 1).

Of the included 35 studies, 20 reported the seroconversion rate in cancer patients after partial COVID-19 immunization (2574 patients) [17, 20, [24] [25] [26] [27] [28] [29] [30] [31] 37, [42] [43] [44] [47] [48] [49] [50] [51] [52] and 24 after complete vaccination schemes (4708 patients). [17] [18] [19] [20] 27, [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] 45, 46, 48, 49, 53, 54] A lower seroconversion rate was achieved by those with incomplete vaccination regimens (51%; 95%CI 41-62) compared to those with fully immunized patients (73%; 95%CI 64-81) (P=0.0009) (Figure 2 

A total of 17 studies that compared seroconversion rates among oncological patients and noncancer controls (9 with incomplete and 13 with complete immunization schemes) were analyzed. Meta-regression analyses revealed that incomplete immunization scheme was a risk factor for lower seroconversion among cancer patients (RR 0.65, 95%CI 0.50-0.86; P=0.003). No significant association was found for vaccine type, and time from last vaccine dose to serologic test (Supplemental eTable 2).

A subgroup analysis was performed including 6 studies that assessed seroconversion rates among patients with solid malignancies compared with non-cancer controls. Four studies assessed patients with incomplete vaccination schemes, [20, 24, 29, 42] with a total of 359 oncological patients and 333 controls.

Compared with non-cancer controls, patients with solid cancer had a 55% reduced likelihood of achieving threshold humoral response after the first dose of a COVID-19 vaccine (RR 0.45; 95%CI 0.37-0.55).

Moreover, in studies evaluating 297 cancer patients who had completed their vaccination regimen, [18, 20, 32, 42] a lower seroconversion rate was documented when compared with 140 controls (RR 0.95; 95%CI 0.92-0.99) (Figure 4) .

In a subgroup analysis of 13 records evaluating humoral seroconversion rates in patients with hematologic malignancies compared to non-cancer controls, 6 included patients with a partial immunization regimen, [20, 27, 30, 44, 48, 51] 7 with a complete scheme, [19, [32] [33] [34] 40, 46, 49] and 4 with both partial and complete vaccination. [20, 27, 30, 48] In the incomplete immunization scheme analysis, of When comparing serological response between types of malignancies after partial immunization, patients with hematological cancer achieved a numerically lower response (49%; 95%CI 35-63) than those with solid tumors (53%; 95%CI 33-72) (P=0.183) (Figure 6 ). When analyzing serological response after complete immunization regimens, patients with hematologic malignancies had a significantly reduced humoral response (65%; 95%CI 57-72) than those with solid cancer (94%; 95%CI 86-97) (P<0.001) (Figure 7) .

In a pooled analysis of 14 studies including patients with hematologic or solid malignancies, [17, 20, 24, [28] [29] [30] [31] 33, 34, 37, 42, 47, 49, 52] immunization (RR 2.04; 95%CI 0.38-11.10) (Figure 8 ).

No meta-analysis was conducted regarding anti-S IgG titers due to the wide heterogenicity in serological immunoassays used in the 8 studies reporting data on this outcome for both patients and controls 

A pooled analysis of 6 studies [20, 25, 26, 39, 40, 54] including 84 patients with incomplete and 634 with complete vaccination regimens showed that 78% (95%CI 30-97) and 60% (95%CI 30-84) developed an adequate T-cell response, respectively (Supplemental eFigure 4).

To the best of our knowledge, this is the first systematic review and meta-analysis assessing the immunogenicity of COVID-19 vaccines in the oncological population. Results of this meta-analysis demonstrate that cancer patients have a lower likelihood of attaining acceptable immune response after COVID-19 immunization when compared to non-cancer patients. However, despite the suboptimal J o u r n a l P r e -p r o o f seroconversion rates observed in this group, a notable increase in humoral response was documented among cancer patients that completed a COVID-19 vaccination regimen.

The low humoral immune response mounted by oncological patients after being vaccinated against SARS-CoV-2 is of utmost importance due to their higher risk of developing severe disease with consequent poor prognosis if infected. [4, 11, 55, 56] Immunization against COVID-19 has been widely recommended among cancer patients, regardless of site of disease, setting, and type of treatment, as its benefits outweigh the potential risks. [55, 57] Oncological patients should be encouraged to adhere to COVID-19 prevention guidelines and complete their vaccination schemes following the recommended intervals between doses (i.e., 3-or 4-weeks for mRNA vaccines). As shown by this meta-analysis, a substantial proportion of patients with cancer do not mount an appropriate immunological response after partial vaccination and could be at a relatively high risk of infection and severe COVID-19 when delaying the second dose.

Furthermore, despite cancer patients having a higher risk of SARS-CoV-2 infection after vaccination compared to controls, only 0.55% of patients developed COVID-19 after being immunized.

These findings are encouraging as they highlight that even though this population has a lower likelihood of mounting an adequate immune response after vaccination, their risk of infection may drop significantly after being vaccinated. However, conclusions should be cautiously drawn as the low rate of infection documented in each study may be influenced by the epidemic burden of COVID-19 across countries and specific time points, as well as the underestimation of SARS-CoV-2 cases due to the lack of testing in asymptomatic participants, which could be as high as 20%, [58] and to an inadequate follow-up.

Growing evidence suggests that among cancer patients, those with hematologic malignancies are less likely to develop robust anti-S IgG after SARS-CoV-2 vaccination due to immunosuppression induced by disease-related lineage defects and its treatments. [3, 17, 35, 36] rates. [17,19, 27-29, 33,34,38-40,42,44-48,51,53,54] Of note, monoclonal antibodies (i.e., anti-CD20) might not only blunt B-cell response by decreasing the neutralizing antibodies titers but may also affect patients' T-cell immunity. [3, 17, 36, 58] Thus, a markedly reduced response to COVID-19 immunization could be expected in patients receiving therapeutic agents that interfere with humoral and cellular response.

Recent data suggest that among patients with suboptimal humoral immunogenicity to COVID-19 vaccines a substantial proportion developed T-cell response, most likely owing to cross-reactivity to other human coronaviruses. [58, 59] Although new evidence from the VOICE and CAPTURE trials have shown that chemotherapy was not a significant predictor for suboptimal immunogenicity in patients with solid tumors, [58, 59] numerous studies have documented the potential detrimental impact that chemotherapy could have in seroconversion rates after COVID-19 immunization in patients with cancer. [17, 18, 20, 25, 30, 33, 35, 38, 41, 46, 54] Further studies with sufficient statistical power to evaluate the influence of different oncologic treatments on COVID-19 vaccine immunogenicity among patients with solid and hematologic malignancies are warranted.

The optimal approach for administering COVID-19 vaccines among patients with higher risk of non-responsiveness remains unclear. According to NCCN guidelines, only patients with stem cell transplant and those receiving cellular therapy should wait for at least three months after finishing the therapy to get vaccinated against COVID-19, otherwise cancer patients should get vaccinated as soon as they can. [57] However, the administration of anti-CD20 monoclonal antibodies within 12 months and chemotherapy within 4 weeks before vaccination could diminish patients' immune response. [17, 19, 27, 28, [38] [39] [40] 58 ,59] Thus, oncologists should warn patients, particularly those with hematological malignancies such as leukemia, lymphoma, multiple myeloma, and those that received COVID-19 vaccines while being under these treatments that they might not have an appropriate protection against SARS-CoV-2 wild-variant and variants of concern. [58] J o u r n a l P r e -p r o o f Several studies have already demonstrated the benefits of a booster COVID-19 vaccine dose after completion of the standard immunization scheme among immunocompromised and cancer patients. [39, [60] [61] [62] [63] [64] Therefore, health authorities in France, Israel, Germany, and the United Kingdom have issued statements advocating for a booster vaccine dose in immunocompromised patients. [17] Additionally, the Food and Drug Administration and the Centers for Disease Control and Prevention have recently authorized the administration of a homologous booster dose for solid organ transplant recipients and those with an equivalent level of immunosuppression. [65, 66] The implementation of this strategy has demonstrated a significant increase in patients' humoral response. [39, 61, 62, 64] Nonetheless, a substantial proportion of the evaluated patients did not attain seroconversion even after receiving a third dose, which could limit the benefits of homologous booster vaccination for immunocompromised patients. [39, [60] [61] [62] 64] Another promising strategy that has gained interest for enhancing patients' immune response after COVID-19 vaccination is the use of heterologous vaccine regimens. Recent studies assessing this approach among the general population have yielded encouraging results, reporting higher anti-S IgG titers and neutralizing antibodies against certain SARS-CoV-2 variants of concern, as well as an increased

CD4 T-cell response compared to homologous COVID-19 vaccine regimens. [67] [68] [69] [70] Clinical investigators, industry, and regulatory stakeholders should encourage the development of clinical and observational studies such as the COV-POPART study [71] that aim to evaluate different immunization approaches in the oncological population, including the use of booster doses and heterologous vaccination schemes.

As the most effective strategy for tackling the burden imposed by the COVID-19 pandemic, immunization should be particularly encouraged among the oncological population. Efforts should also be focused on increasing the available information regarding the effectiveness, safety profile, and benefits of COVID-19 vaccination among cancer patients. Moreover, the promotion of vaccine literacy and the active participation of oncologists and other healthcare workers should be emphasized, as these remain key to increase patients' acceptance and adherence to the recommended vaccination schemes. [72] [73] [74] [75] Despite several countries having removed restrictions like the use of face masks and social distancing for those that have completed their COVID-19 vaccination scheme, these measures should be taken cautiously and should not be extended automatically to all patients with cancer in whom vaccine effectiveness is not comparable to that of the general population.

Among the limitations of this meta-analysis, it should be considered that the number of included studies, as well as the heterogeneity across them regarding patient and control characteristics, patients' type of malignancy and treatment, immunogenicity assessment, and type of vaccine, may limit the generalization of the results. It is particularly important to highlight that the included studies are observational and subject to potential sources of bias, such as selection bias or confounding, that cannot be adjusted through meta-analytical techniques. All included studies evaluated anti-S IgG as a surrogate for COVID-19 immunogenicity, and just a few assessed cellular response or SARS-CoV-2 infection after vaccination.

However, due to the high sensitivity and specificity of most immunoassays and the minimal likelihood of infection in immunized patients, it is reasonable to expect that anti-S IgG levels correlate with neutralizing antibodies against SARS-CoV-2, [17] thus allowing for an adequate COVID-19 effectiveness evaluation. Due to the substantial heterogeneity in immunoassays and threshold values for anti-S IgG measurements, differences in mean titers between cancer patients and controls could not be compared.

The present results have limited generalizability to COVID-19 vaccines different from mRNA BNT162b2, as only a few studies included patients who received other types of vaccines. Although the type of treatment administered in parallel with a COVID-19 vaccine could play an important role in the degree of humoral and cellular responses attained by oncological patients, the lack of sufficient data did not allow to perform subgroup analyses in this regard. Lastly, an important amount of funnel plot asymmetry was detected, particularly towards the null hypothesis. However, the difference in seroconversion rates between cancer patients and controls remained significant after adjusting the pooled effect by limit meta-analysis. As the number of studies in oncological patients increases, robust J o u r n a l P r e -p r o o f methodologies to explore the sources of heterogeneity should be implemented, such as meta-regression, which could help refine our current estimates.

This systematic review and meta-analysis suggests that oncological patients attain a lower immunological response when compared to non-cancer controls. Even after completing the immunization scheme, patients with hematologic and solid malignancies showed inferior seroconversion rates than those without cancer. Despite this suboptimal immunologic response, SARS-CoV-2 infection was documented only in a small percentage of immunized cancer patients. Studies focusing on strategies to enhance the immune response among oncological patients are urgently warranted, as well as those evaluating the effectiveness, feasibility, and optimal timing for this population to receive a booster dose after completing the COVID-19 immunization regimen. Diamonds indicate the meta-analytic pooled RR, calculated separately by vaccination scheme (i.e., partial or complete), and the overall pooled RR (95%CI) in patients with cancer.

Squares represent indirect effect size (Risk ratio [RR]). Horizontal lines indicate 95% Confidence Interval (CI). Diamonds indicate the meta-analytic pooled RR, calculated separately by vaccination scheme (i.e., partial or complete), and the overall pooled RR (95%CI) in patients with cancer.

Squares represent indirect effect size (Risk ratio [RR]). Horizontal lines indicate 95% Confidence Interval (CI). Diamonds indicate the meta-analytic pooled RR, calculated separately by vaccination scheme (i.e., partial or complete), and the overall pooled RR (95%CI) in patients with cancer.

J o u r n a l P r e -p r o o f 

Squares represent indirect effect size (Risk ratio [RR]). Horizontal lines indicate 95% Confidence Interval (CI). Diamonds indicate the meta-analytic pooled RR, calculated separately by vaccination scheme (i.e., partial or complete), and the overall pooled RR (95%CI) in patients with cancer. J o u r n a l P r e -p r o o f

Johns Hopkins Coronavirus Resource Center. COVID-19 Map -Johns Hopkins Coronavirus Resource Center

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Immune responses to COVID-19 vaccines in patients with cancer: Promising results and a note of caution

Mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection with a specific focus on lung and breast cancers: A systematic review and meta-analysis

WHO. WHO Director-General's opening remarks at the media briefing on COVID-19 -3

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial

Randomised Evaluation of COVID-19 Therapy n

Dexamethasone in Hospitalized Patients with Covid-19

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Can COVID vaccines stop transmission? Scientists race to find answers

Impact of solid cancer on in-hospital mortality overall and among different subgroups of patients with COVID-19: a nationwide, population-based analysis

Priority COVID-19 Vaccination for Patients with Cancer while Vaccine Supply Is Limited

Cancer groups urge CDC to prioritize cancer patients for COVID-19 vaccination -The Cancer Letter n

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Safety and Efficacy of J o u r n a l P r e -p r o o f the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer

Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer

Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia

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

COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Immunogenicity of COVID-19 vaccines among patients with cancer: a systematic review and meta-analysis protocol

Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer

Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces high frequency of neutralising antibody and polyfunctional T-cell responses in patients with myeloproliferative neoplasms

Single dose of BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces neutralising antibody and polyfunctional T-cell responses in patients with chronic myeloid leukaemia

Antibody responses after SARS-CoV-2 vaccination in patients with lymphoma

Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study

Weak immunogenicity after a single dose of SARS-CoV-2 mRNA vaccine in treated cancer patients

Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution

The BNT162b2 mRNA COVID-19 vaccine in adolescents and young adults with cancer: A monocentric experience

Seroconversion rates following COVID-19 vaccination among patients with cancer

BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies

Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma

Immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy

Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients

Low rate of seroconversion after mRNA anti-SARS-CoV-2 vaccination in patients with hematological malignancies

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients

Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors

Response to first vaccination against SARS-CoV-2 in patients with multiple myeloma

Impaired antibody response to COVID-19 vaccination in patients with chronic myeloid neoplasms

Correlation between BNT162b2 mRNA Covid-19 vaccine-associated hypermetabolic lymphadenopathy and humoral immunity in patients with hematologic malignancy

Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell directed therapies

Post-Vaccination Anti-SARS-CoV-2-Antibody Response in Patients with Multiple Myeloma Correlates with Low CD19+ B-Lymphocyte Count and Anti-CD38 Treatment

Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia

Response to mRNA vaccination for COVID-19 among patients with multiple myeloma

Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia

Impaired response to first SARS-CoV-2 dose vaccination in myeloproliferative neoplasm patients receiving ruxolitinib

Reduced SARS-CoV-2 infection and death after two doses of COVID-19 vaccines in a series of 1503 cancer patients

Safety and efficacy of BNT162b mRNA Covid19 Vaccine in patients with chronic lymphocytic leukemia

Antibody and J o u r n a l P r e -p r o o f T cell immune responses following mRNA COVID-19 vaccination in patients with cancer

Emerging issues related to COVID-19 vaccination in patients with cancer

Effect of Cancer on Clinical Outcomes of Patients With COVID-19: A Meta-Analysis of Patient Data

COVID-19 Vaccination Guide for People With Cancer

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Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses

Immunogenicity of a heterologous COVID-19 vaccine after failed vaccination in a lymphoma patient

Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients

COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals n

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States n

Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination

Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination

Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination

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Strategies aimed at overcoming COVID-19 vaccine hesitancy among oncologic patients

Supplemental eTable 1. Risk of bias assessment-I (ROBINS-I)

Abbreviations: SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2

Enzyme-linked immunosorbent assay

Squares represent indirect effect size

Diamonds indicate the meta-analytic pooled RR, calculated separately by vaccination scheme (i.e., partial or complete), and the overall pooled RR

Diamonds indicate the meta-analytic pooled RR, calculated separately by vaccination scheme (i.e., partial or complete), and the overall pooled RR (95%CI) in patients with cancer

J o u r n a l P r e -p r o o f