key: cord-0765148-tugmaok6
authors: Tran, Son; Truong, Tony.H.; Narendran, Aru
title: Evaluation of COVID-19 vaccine response in cancer patients: an interim analysis
date: 2021-10-25
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2021.10.013
sha: 819e2c448c47243a7aaf15bd99f481a5056c7da0
doc_id: 765148
cord_uid: tugmaok6

BACKGROUND: Efficacy and safety data of COVID-19 vaccines among cancer populations have been limited; however, preliminary data from recent studies have emerged regarding their immunogenicity and safety in this population. In this review, we examined current peer-reviewed publications containing serological and safety data following COVID-19 vaccination of patients with cancer. METHODS: This analysis examined 21 studies with a total of 5,012 cancer patients, of which 2,676 (53%) had hematological malignancies, 2,309 (46%) had solid cancers, and 739 were healthy controls. Serological responses by anti-SARS-CoV-2 spike protein S1/S2 IgG (anti-S IgG) antibody levels and post-vaccination patient questionnaires regarding vaccine-related side effects following the first and second dose were collected and analyzed. RESULTS: In general, a single dose of COVID-19 vaccine yields weaker and heterogeneous serological responses in both patients with hematological and solid malignancies. Upon receiving a second dose, serological response rates indicate a substantial increase in seropositivity to the SARS-CoV-2 spike protein in all cancer cohorts, but antibody titers remain reduced in comparison to healthy controls. Furthermore, seroconversion in patients with hematological malignancies was significantly lower compared to patients with solid tumors. COVID-19 vaccines are safe and well-tolerated in cancer patients based on current data of local and systemic effects. CONCLUSION: Together, these data support the prioritization of patients with cancer to receive their first and second doses to minimize the risk of COVID-19 infection and severe complications in this vulnerable population. Additional prophylactic measures must be considered for high-risk patients where current vaccination programs may not mount sufficient protection against SARS-CoV-2 infection.

COVID-19, which is caused by the SARS-CoV-2 virus, first emerged in December 2019 and has since led to over 150 million infections worldwide and over four million deaths to date [1] . There is substantial evidence that patients with cancer are at a greater risk of contracting and suffering from severe complications due to viral infections, including COVID-19 [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] . While safety, tolerability, and efficacy data from clinical trials of several vaccines targeting the SARS-CoV-2 virus have been published, limited data are available among patients with active malignancies due to their ineligibility in most studies [13] . Furthermore, a major part of vaccine hesitancy in cancer patients is caused by the lack of efficacy and safety data available for their disease population [14] . Given the widespread immunization of approved COVID-19 vaccines in some countries, safety and immunogenicity data are now emerging for cancer patients. There is an urgent need to inform the recommendations and guidelines for the expedited procurement and delivery of COVID-19 vaccines in vulnerable populations, such as immunocompromised patients with cancer, with the most relevant evidence available. Importantly, these information are critical to aid in the informed decision-making of cancer patients and their family members, along with members of the medical community [15] . In this review, we explore the current evaluation of the immunogenicity and safety of COVID-19 vaccines in patients with cancer.

We searched PubMed for publications from inception to July 14, 2021, using the search terms ("covid 19 vaccines" [MeSH Terms] OR ("covid 19" [All Fields] AND "vaccines" [All Fields]) OR "covid 19 vaccines" [All Fields] OR "covid 19 vaccine" [All Fields]) AND ("cancers" [All Fields] OR "neoplasms" [MeSH Terms] OR "neoplasms" [All Fields] OR "cancer" [All Fields]) AND ("patients" [MeSH Terms] OR "patients" [All Fields] OR "patient" [All Fields]). We reviewed only papers published in English investigating serological and toxicity responses to COVID-19 vaccines in patients with cancer. The final reference list was generated on the basis of their relevance to the scope of this review. Continuous variables were compared using the nonparametric Mann-Whitney U independent samples test.

This review included 21 studies containing serological and/or toxicity data following COVID-19 vaccination in patients with active malignancies. A total of 5,012 patients with active malignancies, of which 2,676 (53%) had hematological malignancies and 2,309 (46%) had solid cancers, and 739 healthy control subjects were analyzed. Clinical J o u r n a l P r e -p r o o f characteristics of the cancer patients and healthy controls are amalgamated and presented in Table 1 . Overall, the median age of the cancer patients ranged from 40-75.5 years, and the majority were men (2,619 [53%] ). Among healthy controls, the median age ranged between 40-81 years. Nineteen out of 21 studies specified patients undergoing cancer-directed therapies, and their treatment types are described (Table  1) . Patients with suspected COVID-19 exposure prior to vaccination were excluded. In general, serological responses were acquired through blood sampling following the first (partial) or second (complete) dose of COVID-19 vaccine and quantified by anti-SARS-CoV-2 spike protein S1/S2 IgG (anti-S IgG) antibody levels. The detection methods for anti-S IgG varied across studies and are described in Tables 2 and 3 . 

Single dose-response rates of BNT162b2 (Pfizer-BioNTech) were assessed in 13 studies [16] [17] [18] [19] [20] [21] 23, 24, [27] [28] [29] [30] 32] , mRNA-1273 (Moderna) in four studies [16, 24, 30, 32] , AZD1222 (Oxford-AstraZeneca) in three studies [18, 19, 24] , and Ad26.COV2.S (Janssen) in one study [33] . Of these, 12 studies classified their cancer patient cohorts (11 cohorts with hematological malignancies, of which three were primarily patients with multiple myeloma [MM] , two of patients with myeloproliferative neoplasms [MPN] , and one study containing patients with chronic myeloid neoplasms [CMN] ; and five cohorts with solid tumors) in addition to seven studies with data from healthy control subjects.

The results from these studies are described in Table 2 , including positive serological response rates (seroconversion) and anti-S IgG antibody titer following partial vaccination. Seroconversion and antibody titer data varied between studies and based on the type of malignancy ( Figure 1A ). After partial COVID- 19 vaccination (second dose). The detection thresholds for positive anti-S IgG antibodies are dependent on the biochemical assay used in each study, which are indicated in Tables 2 and 3 . Pairwise comparisons are based on nonparametric Mann-Whitney U independent samples test.

Toxicity data following vaccination with the BNT162b2 vaccine were available for seven studies [21, 22, 25, 27, 29, 33, 36] , of which three studies contained patients with hematological malignancies [22, 25, 29] (CLL N=167, MM/MPN N=92), two studies with solid tumor patients [21, 36] (N=366), and two studies with a mixed cancer [21, 27] population (N=351). One study included results from healthy controls (N=54). Safety data of the mRNA-1273 and Ad26.COV.S vaccines were discussed in one study [33] . The safety profiles indicate similar experiences between cancer patients and healthy controls with regards to local and systemic effects following partial and complete COVID-19 vaccination ( Table 4 ). The overall local and systemic toxicities and severities after COVID-19 vaccination in patients with cancer are shown ( Figure 2 ). , and severe (prevents daily activity). Each point indicates a study cohort where data was available; the error bars represent the SD of the mean for each category.

Currently, several COVID-19 vaccines have been granted emergency use authorization (EUA) by various national health agencies worldwide. Two mRNA-based vaccines, BNT162b2 produced by Pfizer-BioNTech (known as Comirnaty) and mRNA-1273 by Moderna (known as SpikeVax), have demonstrated significant effectiveness in enhancing immunogenicity against SARS-CoV-2 while maintaining an acceptable safety profile in the general population [37, 38] . In addition, adenovirus-vector vaccines AZD1222 by Oxford-AstraZeneca (known as Vaxzevria) and Ad26.COV2.S by Janssen showed significant efficacy and safety based on ongoing clinical trials [39, 40] . However, these data are unable to inform the unique responses in the cancer population, as most clinical trials have excluded immunocompromised people, including patients with active malignancies [13] . Thus, understanding the efficacy and safety of COVID-19 vaccines in patients with cancer is crucial to guide current vaccination programs.

A number of studies have indicated that cancer patients are at a greater risk of COVID-19 infection and are more likely to develop severe or fatal complications as a result [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] . These might be due to a greater likelihood of comorbidities, disease-related immune dysregulation, or treatment-induced immunosuppressive factors, which have also been shown to negatively affect immunogenicity among patients receiving vaccines, such as for seasonal influenza [41] [42] [43] . It is important to better understand the biological and clinical factors of cancer patients affecting immunological responses to vaccines, especially for COVID-19. These data may be critical in informing the clinical guidelines for the priority vaccination of patients with cancer against this disease [44] [45] [46] [47] . In the present review, we highlight clinical factors that affect seroconversion and indicate that the short-term safety profile of COVID-19 vaccines in cancer patients is safe, well-tolerated, and consistent with the general population.

Based on our analysis, serological response to COVID-19 vaccines within the cancer patient population is significantly reduced in comparison to the healthy population. However, significant differences in response to vaccines are also observed based on the type of malignancy. In prospective studies that include both hematologic and solid cancer patients, patients with hematological malignancies experience disproportionately lower seroconversion for anti-S IgG and reduced antibody titer relative to patients with solid tumors following COVID-19 vaccination. Addeo et al. [16] , observed that 98% of solid tumor patients were seropositive following completed two-dose series of BNT162b2/mRNA-1273 vaccines, compared to 77% of patients with hematological malignancies (p=0.002). Anti-S IgG antibody titer was also reduced after the first dose in hematological cancer patients (median: 6 AU/mL) than that of solid tumor patients (44 AU/mL; p=0.018) and following the second dose (832 AU/mL in hematological malignancies versus 2,500 AU/mL in solid cancers; p=0.029). These observations are supported by findings from the study by Thakkar et al. [33] , which highlighted blunted seropositivity in hematological cancer patients (85%) compared to solid tumor patients (98%; p=0.001), and reduced IgG titers (median: 2,528 AU/mL versus 7,858 AU/mL; p=0.013) following complete vaccination with BNT162b2/mRNA-1273 vaccines. These data supporting differential immunological responses based on malignancy type are consistent with the outcomes following inoculation against seasonal influenza [42] . In general, hematologic cancer patients experience greater immunosuppression, due in part to intrinsic frailty, disease-related immune dysregulation, or by undergoing therapies that can lead to severe myelosuppression and lymphodepletion. These factors contribute to an increased risk of infection and mortality, in addition to poorer immunological responses to vaccination, suggesting that patients with hematological malignancies remain a high-risk patient population until effective vaccination or treatment strategies are available [9, 48, 49] .

Cytotoxic chemotherapies can interfere with DNA replication, synthesis, and cell cycle progression of rapidly proliferating lymphocytes during immune activation, leading to subsequent impairment of the host immune system [50] . Chemotherapy was identified as a significant confounder for poor seroconversion in the study by Palich et al. [28] of solid tumor patients who were on active treatment after a single dose of the BNT162b2 vaccine (odds ratio [OR]: 4.34, 95% CI 1.67-11.30; p=0.003). These observations are supported by findings from Barrière et al. [17] , where solid cancer patients undergoing chemotherapy experienced lower seroconversion (43%; p=0.016) than patients who were chemotherapy-naïve (77%), following the first dose of the BNT162b2 vaccine. Reduced seroconversion was also noted in the study by Addeo et al. [16] , where anti-S IgG titer was significantly lower in patients who received cytotoxic chemotherapy within six months of their first vaccination (median: 611 AU/mL; p=0.019) compared to patients on clinical surveillance (2,500 AU/mL) following a single dose of the BNT162b2/mRNA-1273 vaccines. Hydroxycarbamide treatment was also shown to blunt antibody response in hematologic cancer patients (p=0.018) in the study by Maneikis et al. [25] following two doses of the BNT162b2 vaccine. Given concerns of immunosuppression in patients undergoing chemotherapy affecting seropositivity, current challenges in the optimal timing of COVID-19 vaccination relative to chemotherapy regimens require further analysis to preserve efficacy and reduce confounding risks in such patients [44] . Based on current data, it is recommended that patients scheduled for chemotherapy should receive vaccinations at least three weeks prior to the start of therapy, or between treatment cycles [51, 52] .

Anti-CD20 (rituximab) therapy causes depletion of peripheral B-cells for at least four months following treatment [53] and has been shown to impair vaccination response against influenza or Streptococcus pneumoniae in cancer patients [54] . Accordingly, Herishanu et al. [22] observed that none of 22 CLL patients under anti-CD20 therapy within the last 12 months were seropositive after completed two-dose series with the BNT162b2 vaccine, whereas 46% of CLL patients 12 months or greater post-anti-CD20 therapy showed response (adjusted OR: 37.6, 95% CI 2.2-651.3; p=<0.001). Importantly, 18 of the 22 (82%) CLL patients who were treated with anti-CD20 within 12 months from the study received it in combination with venetoclax. These observations are supported by Re et al. [30] , which found median anti-S IgG titer increase from 0 UI/mL in hematologic cancer patients who underwent anti-CD20 therapy within 12 months to 6.7 UI/mL in patients who were 12 months post-anti-CD20 therapy (p=0.002). Antibody response of the latter was not statistically significant from anti-CD20-naïve patients (16.8 UL/mL; p=0.36) following a single dose of the BNT162b2/mRNA-1273 vaccines. In another study of CLL patients, Roeker et al. [31] identified anti-CD20 treatment within 12 months as a significant clinical factor for poor antibody response post-second dose inoculation with the BNT162b2 vaccine (OR: 0.071, 95% CI 0.013-0.39; p=0.002). Further, Maneikis et al. [25] showed that active anti-CD20 therapy resulted in reduced median anti-S IgG antibody response to two doses of the BNT162b2 vaccine (median: 17 AU/mL; p<0.001) compared to untreated hematologic cancer patients (5761 AU/mL). Together, these findings indicate that recent anti-CD20 therapy (within 12 months of inoculation) is associated with poorer serological response following COVID-19 vaccination.

Plasma cell depleting anti-CD38 (daratumumab) therapy against MM has been previously associated with immunosuppression and heightened susceptibility to infections in treated patients [55] . This is due to a reduction in normal plasma cells following anti-CD38 treatment which leads to a decrease in polyclonal immunoglobulin levels essential for humoral immunity. In the study by Van Oekelen et al. [35] , anti-CD38 treatment in MM patients was associated with non-seroconversion after two doses of the BNT162b2/mRNA-1273 vaccines based on multivariate analysis with corrections (OR: 4.258; p=0.005). Pimpinelli et al. [29] identified active anti-CD38-based therapy in MM patients with reduced response (50%; p=0.003) compared to anti-CD38-naïve MM patients (93%) following inoculation with the BNT162b2 vaccine. While these observations suggest that anti-CD38-based therapy may negatively affect humoral responses in the context of vaccination against SARS-CoV-2, it has been demonstrated that protective antibody induction remains intact for anti-CD38-treated MM patients following inoculations for S. pneumoniae and influenza [56] . Further analysis is needed to identify potential causes for these observed differences, possibly due to biological variabilities produced by the different vaccine platforms (i.e., protein-based versus mRNA-based), by disease-or patient-specific factors, or by differences in therapy regime during vaccine administration.

Other immunosuppressive therapies include chimeric antigen receptor-modified (CAR) T-cell therapy and hematopoietic stem cell transplantation (HSCT). Patients treated with CAR T-cell therapy, in particular CD-19-targeting, experience significant B-cell depletion that can persist for at least six months or longer with resultant hypogammaglobulinemia and heightened risk of infection [57] . In the case of HSCT recipients, extensive immunosuppression and treatment-related complications due to graft-versus-hostdisease (GCVD) has been shown to disproportionately affect susceptibility for infection and mortality due to COVID-19 [58] . Accordingly, Thakkar et al. [33] identified reduced seroconversion in cancer patients who were treated with CAR T-cell therapy (none of three patients responded; p<0.001) or underwent HSCT (73%; p<0.001) following the two-dose series of BNT162b2/mRNA-1273 vaccines.

In general, serological responses are positively correlated with time-lapsed from immunotherapy following reconstitution of humoral and adaptive immunity. Vaccination guidance for patients with planned B-cell depleting treatments (i.e., monoclonal antibody therapy, CAR T-cell therapy, or HSCT) suggest that vaccines be offered at least two weeks prior to beginning treatment, or at least three months following CAR-T cell therapy or HSCT to ensure adequate immune function [44, 51, 52] .

Cancer-directed targeted therapies are designed to act on specific molecular pathways to prevent tumor cell growth and survival, but some of these pathways are also involved in the development, activation, differentiation, and functioning of immune cells, thus "offtarget" immunomodulatory effects can be observed by select targeted agents [59] .

B-cell lymphoma 2 (BCL2) inhibitors (venetoclax) have been associated with cytopenia, specifically lymphopenia and neutropenia, and potential myelosuppression following treatment in leukemia patients, posing an increased risk for infection during the COVID-19 pandemic [60, 61] . In the context of vaccination against SARS-CoV-2, generally poor immunological responses were observed for patients who received venetoclax. In addition to the results from CLL patients with anti-CD20 and venetoclax combination, Herishanu et al. [22] Bruton tyrosine kinase inhibitors (BTKi) are increasingly used in the treatment of CLL and B-cell malignancies, granted the well-defined role of BTK in B-cell receptor (BCR) signaling for the development, proliferation, and survival of B-cell populations [62] . During BTK inhibition, impairment of humoral immunity is observed due to treatmentinduced reduction of normal B-cells followed by decrease in serum IgG levels after 12 months [63] . Herishanu et al. [22] observed that only eight of 50 (16%) CLL patients under active BTKi therapy responded to two doses of the BNT162b2 vaccine. Further, significantly blunted seroconversion in hematologic cancer patients actively treated with BTKi was identified in the studies by Maneikis et al. [25] , where none of 44 patients were seropositive (median IgG: 0 AU/mL; p<0.001), and Roeker et al. [31] , who found that only 32% of BTKi-treated CLL patients seroconverted and identified active BTKi therapy at the time of vaccination as a poor clinical factor for vaccination response (OR: 0.14, 95% CI 0.031-0.60; p=0.009).

Janus kinase 1/2 (JAK1/JAK2) inhibitors (ruxolitinib) have been shown to exhibit immunosuppressive properties by blocking signaling pathways of cytokine receptors, in addition to impairing dendritic cell potentiation and activation of T-cells [64] . In hematologic cancer patients who were actively treated with ruxolitinib, Maneikis et al. [25] observed that these patients mounted blunted serological responses following complete vaccination with the BNT162b2 vaccine (median IgG: 10 AU/mL; p<0.001).

B-cell maturation antigen (BCMA)-targeted therapy is an emerging treatment modality for MM by targeting the overexpression and hyperactivation of BCMA in B-cells of MM patients [65] . Poor antibody response to completed two-dose series of the BNT162b2/mRNA-1273 vaccines in MM patients was significantly correlated with BCMA-targeted therapy (p<0.001) in the study by Van Oekelen et al. [35] . Despite this, little is known about the immunosuppressive properties of BCMA-targeted therapies. Given that anti-BCMA therapies use immunotherapeutic platforms, such as bispecific antibody constructs, antibody-drug conjugates, and CAR T-cells, one could expect that BCMA-targeted therapies may influence immunological outcomes similarly to immunotherapies. More in-depth analysis is required on this topic to identify biological factors related to anti-BCMA therapy and immunological responses to vaccines.

Current vaccination guidance provides no specific timing consideration for patients undergoing targeted therapies and suggests that patients should receive their vaccine at the earliest opportunity available [44] . Based on our review, several anti-cancer targeted therapies negatively affect humoral responses mounted by COVID-19 vaccination in actively treated patients. It is suggested that patients undergoing targeted therapies be monitored for protective antibody titers following immunization to ensure sufficient coverage.

The overall serological response of patients with cancer following COVID-19 vaccination is positive, especially for patients with solid tumors, are younger (<65 years), are not undergoing active therapy, have favourable disease-related factors, and have higher baseline serum immunoglobulin levels at the time of vaccination. However, these findings also highlight the importance of alternative prophylactics for high-risk patient cohorts who may not benefit from current vaccination programs. Recommendations procured by the Infectious Disease Society of America (IDSA) suggest that vaccinations during immunosuppressive states, including those administered during active chemotherapy, should not be considered valid doses unless an antibody titer level sufficient for protection is demonstrated [66] . Thus, patients with suboptimal vaccine responses represent a need for prospective studies to establish additional immunization strategies to enhance coverage [49] (i.e., herd immunity, using different vaccine types or booster vaccinations) or alternative pharmacological (i.e., neutralizing monoclonal antibodies [67] ) and non-pharmacological interventions (i.e., mask-wearing, physical distancing) to mitigate the risk of SARS-CoV-2 infection. [18, 34] Immunoparesis [18, 32] Lymphopenia [35] Increasing lines of treatment [34, 35] Heightened pre-vaccination lactate dehydrogenase (LDH) levels [34] 

It is important to consider the safety of COVID-19 vaccines in patients with active malignancies, given their exclusion from earlier clinical studies. Overall, the short-term safety profile of COVID-19 vaccines in patients with cancer appears to be consistent with previous findings in healthy populations [37, 38, 40] . The majority of local and systemic effects reported were mild to moderate in severity, with localized pain at the injection site, myalgia, and fatigue being the most commonly reported. Across the seven studies analyzed, adverse events related to elevated liver enzyme levels were documented in 24 patients [21] , deranged liver function tests of unknown cause in one patient [27] , and newly documented regional cervical or axillary lymphadenopathy in 5% of patients undergoing computed tomography (CT) or positron emission tomography (PET) scans during routine care [21] . No differences in the safety profiles of cancer patients with hematological or solid malignancies were observed [27] . Patients undergoing active treatment showed no difference in side effects experienced compared to those who were treatment-naïve [22] , and those treated with immune checkpoint inhibitors (ICIs) did not experience any serious adverse events or additional side effects in combination with immunotherapy following vaccination [36] . We believe that these data provide a safety signal for cancer patients to receive a COVID-19 vaccine as soon as possible. Continued safety monitoring of cancer patients with COVID-19 vaccines is required to fully assess the long-term effects on safety, in addition to ongoing disease and treatment progression for this population.

Firstly, the limited number of patients included in each study may adversely affect the power to distinguish differential responses between cancer cohorts and within cancer subgroups. Certain predictors of response may be statistically insignificant due to the lack of statistical power to resolve them. We encourage collaborative efforts between institutions for large-scale studies to overcome the bias issues related to low-powered analyses. Secondly, while antibody-mediated responses to the vaccines may play a crucial role in immunity [68] , evaluations into cellular immunity towards SARS-CoV-2 should also be considered [69] . Only two studies [23, 27] included in this review examined T-cell responses following immunization, and none were able to observe further adaptive immune responses due to the short timeframe. Furthermore, certain immunomodulating cancer-directed therapies, such as ICIs, may confer advantageous responses in mediating cell-based immunogenicity following vaccination [70] . Immunological memory is a hallmark of protective immunity after vaccination, and studies describing the effects of COVID-19 vaccines on memory B-cells, CD8 + and CD4 + T-cells in cancer patients, especially after immunomodulating treatments, should be forthcoming [71] . Thirdly, experimental differences may impact the robustness of the findings in this review, as studies used different assay platforms to quantify antibody responses, samples were collected at varying time points, and the recruited patients and healthy controls may be affected by convenience sampling biases. Fourthly, efficacy data of COVID-19 vaccines in cancer patients against emerging variants of concern is limited and partial immunogenic escape of SARS-CoV-2 variants of concern has been observed in vaccinated individuals [72] . Further, breakthrough of SARS-CoV-2 infection in fully vaccinated patients, particularly those with hematological malignancies, have been documented [24, 25] , thus emphasizing the urgent need for additional prophylactic measures against infection for these high-risk populations. Lastly, the effects of COVID-19 vaccines on pediatric, adolescent and young adult (AYA) cancer patients have not been sufficiently elucidated [73] and should be importantly considered.

In summary, this study sought to capture the most current data on the safety and immunogenicity of COVID-19 vaccines in patients with cancer, to urgently inform cancer and public health communities regarding this important topic. Encouragingly, a number of clinical trials are currently underway to assess the outcomes of cancer patients who are receiving vaccination against SARS-CoV-2 (ClinicalTrials.gov: NCT04865133, NCT04715438, NCT04746092). Once these data are available, they may allow us to better understand the effects of cancer and cancer-directed therapies in relation to immunogenicity and safety towards current and future vaccines. Our interim findings reinforce significant considerations for cancer patients to be a high-priority subgroup for COVID-19 vaccination and emphasises the need for longer-term data. For high-risk patients, alternative prophylactic measures are urgently needed and strategies to optimize vaccination coverage should be thoroughly explored [49] . Continued vigilance towards public health measures should be exercised by patients with cancer, their caregivers, and the general population at large, to better protect vulnerable populations from infection.

WHO Coronavirus Disease (COVID-19) Dashboard 2021

COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Realworld assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID-19 disease) in patients with multiple myeloma receiving systemic anti-cancer therapy

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers

Outcomes of COVID-19 in patients with CLL: a multicenter international experience

Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study

SARS-CoV-2 infection in the Italian Veneto region: adverse outcomes in patients with cancer

Determinants of COVID-19 disease severity in patients with cancer

Mortality in patients with cancer and coronavirus disease 2019: A systematic review and pooled analysis of 52 studies

Mortality in hospitalized patients with cancer and coronavirus disease 2019: A systematic review and meta-analysis of cohort studies

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

Commentary: SARS-CoV-2 vaccines and cancer patients

Acceptance of SARS-CoV-2 vaccination among French patients with cancer: a cross-sectional survey

Adherence to COVID-19 vaccines in cancer patients: promote it and make it happen

Immunogenicity of SARS-CoV-2 messenger RNA Vaccines in Patients with Cancer

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

High levels of anti-SARS-CoV-2 IgG antibodies in previously infected patients with cancer after a single dose of BNT 162b2 vaccine

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

Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia

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

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

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

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

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

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

Fifthweek 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

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

COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia

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

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

Short-term safety of the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

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

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine

Influenza Immunization of Adult Patients with Malignant Diseases

Influenza Vaccine Effectiveness Among Patients With Cancer: A Population-Based Study Using Health Administrative and Laboratory Testing Data From Ontario, Canada

Responses of patients with neoplastic diseases to influenza virus vaccine

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

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

SARS-CoV-2 vaccines for cancer patients: a call to action

The ESMO Call to Action on COVID-19 vaccinations and patients with cancer: Vaccinate. Monitor. Educate

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Current perspectives for SARS-CoV-2 vaccination efficacy improvement in patients with active treatment against cancer

Lymphopenia in Cancer Patients and its Effects on Response to Immunotherapy: An opportunity for combination with Cytokines?

SARS-CoV-2 vaccines for cancer patients treated with immunotherapies: Recommendations from the French society for ImmunoTherapy of Cancer (FITC)

ASH-ASTCT COVID-19 vaccination for HCT and CAR T cell recipients 2021

Effective B cell depletion with rituximab in the treatment of autoimmune diseases

The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab

Infectious complications and NK cell depletion following daratumumab treatment of multiple myeloma

Effect of daratumumab on normal plasma cells, polyclonal immunoglobulin levels, and vaccination responses in extensively pretreated multiple myeloma patients

Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy

Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study

Combining immunotherapy and targeted therapies in cancer treatment

Treating Leukemia in the Time of COVID-19

Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial

Bruton's tyrosine kinase: an emerging targeted therapy in myeloid cells within the tumor microenvironment

BTK Inhibitors in Cancer Patients with COVID-19: "The Winner Will be the One Who Controls That Chaos

The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo

B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches

IDSA clinical practice guideline for vaccination of the immunocompromised host

Neutralizing monoclonal antibodies for treatment of COVID-19

Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

Cell-Mediated Immunogenicity of Influenza Vaccination in Patients With Cancer Receiving Immune Checkpoint Inhibitors

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees

BNT162b2 mRNA Covid-19 Vaccine in AYA with cancer: a monocentric experience

We acknowledge the support of the Kids Cancer Care Foundation of Alberta and the Alberta Children's Hospital Foundation.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

None declared.J o u r n a l P r e -p r o o f

J o u r n a l P r e -p r o o f Highlights -Efficacy and safety data of COVID-19 vaccines are emerging for patients with cancer -Vaccination yields weaker and heterogeneous serological response in cancer patients -Seroconversion in hematologic cancer patients is reduced after complete vaccination -Antibody titers in cancer patients remain blunted compared to healthy controls -Safety profile of COVID-19 vaccines in cancer patients is safe and well-tolerated J o u r n a l P r e -p r o o f

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:J o u r n a l P r e -p r o o f