Skip to main content
Download PDF

Incidence of severe adverse events in cancer patients after treatment with immune-checkpoint inhibitors during the COVID- 19 pandemic

BMC Immunology volume 26, Article number: 33 (2025) Cite this article

Abstract

Immune-checkpoint inhibitors (ICIs) can cause inflammation and immune-related adverse events (irAEs). Although irAEs may be caused by dysregulation of cytokines, the impact of various COVID- 19-related factors on expression of ICI-related AEs remains unclear. Assessment of AEs following ICI administration during the COVID- 19 pandemic may provide valuable insights that enable optimization of patient selection, thereby maximizing the benefits of ICI therapy. The aim of this study was to investigate the actual occurrence of severe AEs after ICI administration during the COVID- 19 pandemic. The medical records of patients who received ICI at Saga University Hospital were examined retrospectively. The primary endpoint was the incidence of all AEs ≥ Grade 3 that occurred after ICI administration. The survey period, from Jan 2020 to Dec 2022, was divided into an earlier (Jan 2020–March 2021) and a later (April 2021–Dec 2022) period. AEs with a clear cause other than ICI were excluded from the analysis. A total of 527 patients were included in the analysis, with a median follow-up of 422 days. During the COVID- 19 pandemic, the incidence of AEs ≥ Grade 3 after ICI administration was 52.8%. The incidence of AEs ≥ Grade 3 AEs after ICI administration was significantly higher during the later period [23.4% (57/244) in the earlier period and 49.8% (236/474) in the later period; mixed effect model p < 0.0001, odds ratio, 3.37 (95% CI: 2.32–4.89)]. Overall survival was significantly worse in the group with AEs ≥ Grade 3 than in the group without AEs ≥ Grade 3 [HR (95% CI) = 0.48 (0.36–0.65), p = 0.0001]. During the COVID- 19 pandemic, it became clear that the incidence of severe AEs (including irAEs) increased after ICI administration, particularly during the later period of the disease. Various factors may be associated with occurrence of severe AEs after ICI administration, and long-term careful observation and prospective multicenter clinical studies are required.

Peer Review reports

Introduction

Recently, antibodies specific for cytotoxic T lymphocyte-associated antigen- 4 (CTLA- 4), programmed cell death- 1 (PD- 1), and programmed cell death ligand- 1 (PD-L1) were introduced into clinical practice as cancer chemotherapy. Immune-checkpoint inhibitors (ICIs) trigger strong activation of anticancer immune responses; however, there is a risk that they also activate an immune response against autologous tissues. Injury to autologous tissues via this type of immune response is referred to as an immune-related adverse event (irAE), and it can occur in various organs of cancer patients due to an adverse reaction to cancer immunotherapy. The history of cancer treatment, encompassing cytotoxic agents, molecularly-targeted therapies, and combination regimens, has deepened our understanding of irAEs and continues to inform future therapeutic strategies [1].

Infection with coronavirus SARS-CoV2 (COVID- 19 disease) remains a threat worldwide, and cancer patients are at particularly high risk for severe COVID- 19-related illness, respiratory failure, and death [2,3,4]. Furthermore, the COVID- 19 pandemic limited access to medical care, resulting in delays in treatment and an increased risk of cancer progression and other complications [5, 6]. Such delays may have a decisive impact on prognosis, especially for patients who require time-critical treatments such as surgery and chemotherapy. Furthermore, the impact of the virus on immunomodulation may pose significant risks. Cancer patients are at particularly high risk of becoming infected with COVID- 19 due to their weakened immune systems; therefore, they were prioritized for COVID- 19 vaccination [6]. There was a concern that the COVID- 19 vaccine itself may cause cytokine release syndrome during ICI treatment; however, the effects of particular COVID- 19 variants on occurrence of AEs after ICI are not clear [7].

Although irAEs may be caused by dysregulation of cytokines, the impact of various COVID- 19-related factors on expression of ICI-related AEs remains unclear. The combination of COVID- 19 vaccination and ICIs in cancer patients has the potential to enhance immunological stimulation, possibly yielding reciprocal benefits; however, given the distinct immunomodulatory effects of both interventions, concerns have been raised regarding the potential for increased irAEs and other unintended interactions [8]. Assessment of AEs following ICI administration during the COVID- 19 pandemic may provide valuable insights that enable optimization of patient selection, thereby increasing the proportion of individuals who will benefit from ICI therapy [1].

The aim of the present study was to investigate the real incidence of severe AEs after ICI administration from January 1, 2020, to December 31, 2022, during the COVID- 19 pandemic. We attempted to collect data regarding all AEs that occurred in patients after ICI administration over time, and so did not adhere to the strict definition of irAEs.

Patients and methods

Patients

The present study involved a retrospective review of the medical records of 539 patients who received any ICIs at Saga University Hospital from January 2020 to December 2022. ICIs included ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The following patients who could not be evaluated for AEs after ICI administration were excluded: 11 patients who were transferred to another hospital after two or fewer ICI doses, and one patient who suddenly stopped attending the hospital (reason unknown) (Fig. 1).

Fig. 1
figure 1

Flow chart outlining the study. COVID-19 era (Jun.2020-Dec.2022)

Full size image

To enable a longitudinal comparison, including data from non-COVID- 19 periods, an additional analysis was conducted on patients from 2019 who met the study inclusion criteria.

Data collection and outcome assessment

The primary endpoint was the incidence of all ≥ Grade 3 AEs that occurred after ICI administration. The end of the follow-up period was December 31, 2023. Data extracted from the medical records of eligible patients included age, sex, diagnosis, cancer type, complications, treatment history, medication history, and AEs.

AEs were defined as any medical event occurring in patients who received an ICI, including unintended signs, symptoms, illnesses, or abnormal test results, regardless of causality. AEs with a clearly documented causal relationship unrelated to ICI in the medical record were excluded. The following events were excluded: AEs of non-ICI drugs, including hematologic toxicity and other complications from antineoplastic agents administered after the ICI (when explicitly documented in the medical record); complications definitively associated with the underlying disease, such as tumor progression and post-surgical complications; events with an explicitly documented alternative cause in the medical record; and non-emergency hospital admissions, including those for scheduled surgery, radiotherapy, or palliative care for symptoms with a clear etiology. Collected AEs were categorized based on their clinical significance and impact according to the Common Terminology Criteria for Adverse Events (CTCAE) and guidelines for irAEs [9,10,11]. The affected organ systems included the neuromuscular, cardiac and vascular, respiratory, gastrointestinal, hepatobiliary, renal, skin, endocrine, blood and lymphatic system, and others. The severity of AEs was assessed according to the CTCAE version 5.0, and guidelines for irAE [9,10,11]. The definitions, exclusion criteria, categorization, and assessment criteria for AEs are presented in Supplementary Table 1.

The present study was approved by the Clinical Research Ethics Review Committee of Saga University Hospital (Saga University Clinical Research Review Board; Approval No.: 2023-12-02), and was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki. The need for informed consent was waived owing to the retrospective nature of the study. The official website of the institution was used to allow patients to opt out from participation.

Statistical methods

Kaplan–Meier analysis was used to estimate the cumulative incidence of ≥ Grade 3 AEs after ICI administration from January 2020 to December 2022. In Japan, the number of COVID- 19 cases peaked in 2022, and the COVID- 19 vaccination program was initiated in April 2021. Therefore, the incidence of all AEs ≥ Grade 3 that occurred after ICI administration were analyzed separately during the earlier (from January 1, 2020 to March 31, 2021) and later (from April 1, 2021 to December 31, 2022) periods. A mixed-effects model was used for group comparisons when two groups of nonidentical patients and two groups of identical patients were mixed. The χ2 test (Fisher's exact test for expected frequencies of 5 or less) was used to assess differences in the incidence of ≥ Grade 3 AEs between the earlier and later periods; this test was used to compare data from two groups that did not contain the same patients. The McNemar test was used to compare two groups that did contain the same patients. Survival probability was estimated using the Kaplan–Meier method, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a Cox proportional hazards model. Statistical analysis was performed using JMP (17.2), and a P value < 0.05 was deemed significant.

Results

Patient characteristics

Overall, 527 patients were included in the analysis, with a median follow-up of 422 days (1–1455 days). The median age was 70 years (17–90), and 72.3% of the cohort were male. The most common primary tumor was respiratory, followed by head and neck, and gastrointestinal tract. The background of the eligible patients, including their ICI regimens, is shown in Table 1.

Table 1 Patient characteristics
Full size table

The study design, in which the COVID- 19 pandemic period was divided into an earlier (from January 1, 2020 to March 31, 2021) and a later (from April 1, 2021 to December 31, 2022) period, is shown in Supplement Fig. 1. Of the total 527 patients included in the analysis, the earlier period group (244 patients) included 53 patients who could not be followed in the later period (after April 2021) due to death or transfer by March 31, 2021, and 191 patients who could be followed in the later period (121 of whom continued receiving ICI during the later period). The later period group (474 patients) included the 191 patients who were followed during both the earlier and the later periods, as well 283 patients who began taking ICI during the later period.

Incidence AEs ≥ Grade 3 after ICI administration

During the entire study period (from Jan 2020 to Dec 2022), 52.8% (278/527) of patients experienced at least one AE of ≥ Grade 3 after ICI administration. The incidence of AEs ≥ Grade 3 in the combined with ICI anti-CTLA- 4 antibody group was significantly higher than that in the uncombined anti-CTLA- 4 antibody group [66.1% (37/56) vs. 51.2% (241/471), respectively; χ2 test p = 0. 0347].

The trend in the incidence and number of ≥ Grade 3 AEs relative to the number of patients treated with ICI per month from January 2020 until December 2022 is shown in Fig. 2. Various differences were observed regarding the timing and number of AEs ≥ Grade 3 after administration of ICIs. For example, there were cases in which AEs ≥ Grade 3 occurred not only during the period of ICI administration, but also during several months after the end of ICI administration, as well as single patients in which multiple types and numbers of AEs ≥ Grade 3 occurred. AEs ≥ Grade 3after ICI administration included neuromuscular disorders (meningitis, myositis, seizures, neuropathy, weakness), cardiac and vascular disorders (stroke, heart failure, myocardial infarction, myocarditis, thrombosis), respiratory disorders (pneumonia, pleural effusion, respiratory distress), gastrointestinal disorders (gastrointestinal perforation, stomach/enteritis), hepatobiliary disorders, renal disorders, skin disorders, endocrine disorders (pituitary dysfunction, adrenocortical dysfunction, thyroid dysfunction, type 1 sugar diabetes), blood and lymphatic system disorders (thrombotic thrombocytopenic purpura, autoimmune anemia, lymphomatosis), and “other” disorders (i.e., various symptoms requiring hospitalization and treatment, including fatigue, or death within 1 month of ICI administration). The cumulative incidence curve for first-time AEs ≥ Grade 3 after administration of ICI from January 2020 until December 2022 is shown in Fig. 3. Overall, first-time AEs ≥ Grade 3 occurred in 265 patients from a population of 472 (excluding 55 patients who received an ICI prior to January 1, 2020, for whom the onset date of their first AE was unknown [527–55 = 472]). All AEs are shown in Fig. 3A, and the different AE categories are shown in Fig. 3B. Both panels show events occurring from January 2020 through December 2022, with a potential increase in incidence observed during the later period (after April 2021). Overall survival (OS) was significantly worse in the group with AEs ≥ Grade 3 than in the group without AEs ≥ Grade 3 [HR (95% CI) = 0.48 (0.36–0.65), p = 0.0001]; Fig. 4).

Fig. 2
figure 2

Occurrence of AEs ≥ Grade 3 after administration of ICI and changes in incidence of AEs ≥ Grade 3 over time after administration. In Japan, the number of COVID- 19 cases peaked in 2022, and COVID- 19 vaccination was initiated in April 2021. The history of ICI approvals in Japan is shown in Supplementary Table 2. Monthly percentage of patients with AEs ≥ Grade 3 after treatment with ICI, and the number of AEs in each category: 1. Blue: respiratory disorders. 2. Green: hepatobiliary disorders. 3. Red: cardiac and vascular disorders. 4. Brown: gastrointestinal disorders. 5. Yellow: endocrine disorders. 6. Purple: neuromuscular disorders. 7. Beige: skin disorders. 8. Pink: blood and lymphatic system disorders. 9. Light blue: renal disorders. 10. Gray: other disorders

Full size image
Fig. 3
figure 3

Cumulative incidence of first-time AEs ≥ Grade 3 after January 2020. a All AEs ≥ Grade 3, b Category of AEs ≥ Grade 3. The figure shows the cumulative incidence of the first-time AEs ≥ Grade 3 occurring after ICI administration during a 3-year period from January 1, 2020 to December 31, 2022. Overall, first-time AEs ≥ Grade 3 occurred in 265 patients from a population of 472 (excluding 55 patients who received an ICI prior to January 1, 2020, and for whom the onset date of their first AE was unknown [527–55 = 472). The vertical line at 456 days corresponds to April 1, 2021. The shaded area shows the 95% confidence interval

Full size image
Fig. 4
figure 4

Influence of AE onset on patient prognosis. Kaplan–Meier curve analysis depicting overall survival (OS) of patients with or without AEs ≥ Grade 3 after ICI administration. All patients with AEs ≥ Grade 3  and without AEs ≥ Grade 3  

Full size image

The incidence of AEs ≥ Grade 3 after ICI administration increased significantly during the later period; 23.4% (57/244) in the earlier period vs. 49.8% (236/474) in the later period [mixed-effects model, p < 0.0001; odds ratio, 3.37 (95% CI: 2.32–4.89); Fig. 5). Furthermore, analysis limited to the 191 patients who were followed up both before and after April 2021 showed that the incidence rate of AEs ≥ Grade 3 after ICI administration increased significantly during the later period (15.2% (29/191) in the earlier period vs. 42.4% (81/191) in the later period; McNemar test, p < 0.0001). In the same 191 patients, combined use of anti-CTLA- 4 antibody during the later period also increased significantly. Similarly, in the different patient groups, the incidence of AEs ≥ Grade 3 after ICI administration increased significantly during the later period, regardless of concomitant use of an anti-CTLA- 4 antibody (Supplementary Table 1).

Fig. 5
figure 5

Incidence of AEs ≥ Grade 3 after ICI administration during the earlier and later periods. (Mixed-effects model). In all patients during the earlier period  and later period . In Japan, the number of COVID- 19 cases peaked in 2022, and COVID- 19 vaccination was initiated in April 2021. The history of ICI approvals in Japan is shown in Supplementary Table 2

Full size image

For longitudinal comparison, the background of the eligible patients, including their ICI regimens in 2019 (the period prior to COVID- 19), is presented in Supplementary Table 3. In 2019, the incidence of AEs ≥ Grade 3 after ICI administration was 31.0% (44/142) across all regimens, and 50.0% (2/4) for anti-CTLA- 4 antibody combination therapy (Supplementary Fig. 2). The number of AE reports following ICI administration, as well as the proportion of ICI-related reports relative to all reported drugs in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), from January 2019 to March 2022 are shown in Supplementary Fig. 3. The number of AE reports in which ICIs were identified as the primary suspected (PS) or secondary suspected (SS) agents demonstrated an increasing trend, starting from the third quarter of 2021. Additionally, the proportion of ICI-related reports relative to all reported drugs showed a slight increase during the fourth quarter of 2021.

Discussion

In the present study, the incidence of AEs ≥ Grade 3 during the entire period of ICI administration during the COVID- 19 pandemic period was 52.8%. Although the methods used to evaluate AEs vary between studies, the data suggest that the incidence of serious AEs after ICI administration range from 10–75%, with the incidence of serious irAEs ranging from 10–30% [12,13,14,15,16]. Although there are various guidelines for managing irAEs [9, 11, 17], these AEs may be latent in conditions that are difficult to define and classify, such as fatigue and neuropathy [18]; therefore, careful long-term observation and evaluation of all AEs after ICI administration may help to prevent and/or treat serious irAEs. In the present study, we found that patients with Grade 3 or higher irAEs had a significantly worse prognosis than those without irAEs. Meanwhile, a meta-analysis of randomized controlled trials evaluating the association between irAE incidence and OS reported no clear correlation overall; however, in the melanoma trial subset, there was a negative association between treatment effects and gastrointestinal Grade 3–4 irAEs, and treatment effects and OS [19]. Conversely, other studies suggest that irAEs may contribute to improved OS, even in cases with severe irAEs, without compromising survival benefits [14]. The relationship between irAEs and OS likely varies depending on the evaluation method and patient-specific factors; therefore, careful long-term observations and further investigations are warranted to clarify this complex interplay.

The incidence of AEs ≥ Grade 3 after ICI administration increased throughout the study period, but especially after April 2021 (Figs. 2, 3, and 5). Furthermore, the comparison limited to the identical patients and different patients who could be followed before and after April 2021 revealed that the incidence of AEs ≥ Grade 3 after ICI administration was significantly higher during the later period (after April 2021) (Supplementary Table 4). Even within FAERS, the number of AE reports following ICI administration from January 2019 to March 2022 showed an upward trend, starting from the second quarter of 2021 (Supplementary Fig. 3). A report analyzing irAEs listed in the VigiBase, an international pharmacovigilance database containing information reported from 2008 to January 2023, noted a steep increase in myotoxicity (i.e., myocarditis, myositis, myasthenia gravis) and pancreatico-hepatic irAEs from 2021–2022, although there was a general decline after 2020 [20]. Furthermore, a recent study suggests an increase in the prevalence of ICI-mediated muscle damage, including myositis and myocarditis, in the COVID- 19 era [21]. With respect to hepatitis and dysautonomia, drug safety surveillance analyses have also been conducted using FAERS [22, 23], which reported an annual increase in ICI-induced thrombocytopenia from 2012–2022 [24]. These studies suggested that multiple risk factors and clinical peculiarities related to specific irAEs can be identified as “signals” that may guide clinical practice and future research [20].

In Japan, the combination of ICI and chemotherapy was approved in December 2018, and is now indicated for use in clinical practice in combination with cytotoxic drugs such as platinum-based drugs, and molecular targeted drugs such as bevacizumab (Supplementary Table 2). The background characteristics of patients receiving ICIs in 2019 suggest substantial differences in application of combination regimens involving anti-PD-(L)1 and anti-CTLA- 4 antibodies, as well as chemotherapy, as well as in differences in treatment lines (Supplementary Table 3). For example, a higher proportion of patients in the 2019 cohort received ICIs as the 3rd line or later drug when compared with the 2020–2022 cohort (32.4% in 2019 vs. 16.2% in 2020–2022), suggesting that a higher proportion of patients in the 2019 cohort had terminal cancer. By contrast, in the 2020–2022 cohort, the use of anti-CTLA- 4 antibodies, as well as the proportion of patients receiving combination therapy (ICI plus chemotherapy), increased. These factors may have influenced the incidence rate of AEs. Therefore, careful consideration of patient background is essential when interpreting the incidence of AEs following ICI administration. In addition, January 2020 marked the start of the COVID- 19 pandemic, and a COVID- 19 vaccination campaign was launched in April 2021, with approximately 80% of the population receiving the vaccine. The retrospective nature of the study means that it was not possible to accurately investigate COVID- 19 infection (including subclinical infections) and COVID- 19 vaccination status in the patients enrolled in the present study.

Around April 2021, various ICI regimens began to be used in clinical practice in Japan. Anti-CTLA- 4 therapy enhances tumor immune responses by inhibiting the immune-checkpoint molecule CTLA- 4 on T cells, thereby promoting T-cell activation and proliferation. By contrast, anti-PD-(L)1 therapy restores T-cell anti-tumor activity by blocking the PD- 1/PD-L1 pathway, which is mediated by tumor cells and immunosuppressive cells. Combined use of anti-CTLA- 4 and anti-PD-(L)1 agents increases the risk of early onset and severe irAEs due to multilayered activation of the immune response. In particular, the incidence of skin disorders, gastrointestinal symptoms (e.g., colitis) and endocrine disorders (e.g., pituitary inflammation) increases significantly [13, 25]. Notably, Grade 3 or higher irAEs are more frequent in those receiving CTLA- 4 monoclonal antibodies (mAbs) than in those receiving PD- 1 inhibitors (31% vs. 10%, respectively), highlighting the need for careful monitoring and management when utilizing these therapies in combination [26]. One of the reasons for the increased incidence of AEs after ICI administration may be the concomitant use of anti-CTLA- 4 antibodies; however, the incidence of ≥ Grade 3 AEs after ICI administration increased markedly around April 2021, regardless of the concomitant use of anti-CTLA- 4 (Supplementary Table 4). These results suggest that other factors, which were not identifiable in this study, might be contributing to the increase in AEs ≥ Grade 3 after ICI administration.

It is likely that subclinical infection of cancer patients with COVID- 19 caused complications [27,28,29]. COVID- 19 predisposes to acute respiratory distress syndrome, and the risk may be higher in cancer patients. Cancer patients are at increased risk for thrombosis, which can also be exacerbated by COVID- 19, as well as organ damage due to overproduction of cytokines in response to infection. As mentioned earlier, the COVID- 19 pandemic in Japan began in 2020, and COVID- 19 vaccinations became available in April 2021. Cancer patients are at increased risk of complications from SARS-CoV- 2 infection [4, 6, 30], and so vaccination is recommended; however, data regarding the safety of COVID- 19 vaccines in cancer patients receiving chemotherapy or immunotherapy are limited [31]. Studies that have examined the safety of cancer patients who received ICI after COVID- 19 vaccination suggest that the vaccine is safe “in the short term” [32,33,34,35,36,37]; however, case reports suggest that severe irAEs such as cytokine release syndrome, acute myocarditis, psoriasis, hepatitis, and diabetic ketoacidosis have occurred immediately after administration of the COVID- 19 vaccine to cancer patients who had received ICIs [7, 38,39,40,41,42,43,44]. Furthermore, anti-CTLA- 4-deficient patients have suffered mild COVID- 19 infections and experienced AEs after receiving a COVID- 19 vaccine [45]. These findings suggest that careful long-term observation of the safety of COVID- 19 vaccines in cancer patients treated with ICI should continue.

The present study has several limitations. Although we tried to minimize recall bias and inconsistencies in medical record documentation, and AEs were evaluated using the CTCAE, and irAEs were determined in accordance with ASCO and ESMO guidelines, the retrospective nature of the study introduces inherent limitations that affect the reliability of AEs classification, and the completeness of the data. Additionally, distinguishing AEs caused by ICIs from those related to cancer progression, other treatments, or underlying disease remains a significant challenge. Importantly, in the context of this study, factors such as COVID- 19 vaccination and subclinical infections were not evaluated comprehensively. Therefore, while an increase in AEs was observed during the COVID- 19 era, it cannot be concluded definitively that this rise is attributable to COVID- 19 infection or vaccination. Additionally, we could not fully exclude the influence of other confounding factors such as healthcare delays, changes in treatment policy, or pandemic-related psychological stress. This study only demonstrates the fact that AEs increased at a single center in Japan during a specific period; the potential impact of regional healthcare system differences during the pandemic were not evaluated. A lack of prospective data collection undermines the study’s conclusions about long-term trends in AE incidence and causative factors. Predictive biomarkers for irAEs, such as cytokine profiles and T-cell activation markers, have been explored to optimize ICI therapy [46, 47]. To reduce the risk of irAEs, regular measurement of biomarkers and monitoring of AEs through X-rays and ECG testing is required. In addition, to ensure prompt and efficient collaboration in the event of irAEs, it is crucial to develop treatment algorithms in collaboration with other specialists. To mitigate the risk of AEs during a pandemic, enhanced monitoring protocols, including more frequent follow-up visits, proactive screening for infections, and early detection of irAEs, could potentially improve patient outcomes. Additionally, considering patient-specific factors and pandemic-related constraints, adjusting ICI regimens (e.g., modifying dosing intervals or selecting ICI combinations with a lower risk profile for AEs) may be beneficial. Future research should evaluate the effectiveness of these strategies in reducing severe AEs while maintaining treatment efficacy. Future prospective multicenter clinical studies that collect accurate data on cancer progression, comorbidities (e.g., immune-related comorbidities), organ function, biomarkers, immune function, infection, concomitant medications, and vaccination status are desirable.

In conclusion, the real-world data reported herein show that long-term severe AEs occur at a high frequency after ICI administration. In addition, the number of severe AEs after ICI administration increased after April 2021. Various factors may be associated with the occurrence of AEs ≥ Grade 3 after ICI administration, and so long-term careful observation and prospective multicenter clinical studies are required in the future.

Data availability

No datasets were generated or analysed during the current study.

References

  1. Sonkin D, Thomas A, Teicher BA. Cancer treatments: Past, present, and future. Cancer Genet. 2024;286–287:18–24. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.cancergen.2024.06.002.

    Article  CAS  PubMed  Google Scholar 

  2. Chavez-MacGregor M, Lei X, Zhao H, Scheet P, Giordano SH. Evaluation of COVID-19 Mortality and Adverse Outcomes in US Patients With or Without Cancer. JAMA Oncol. 2022;8(1):69–78. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamaoncol.2021.5148.

    Article  PubMed  Google Scholar 

  3. Hosseini-Moghaddam SM, Shepherd FA, Swayze S, Kwong JC, Chan KKW. SARS-CoV-2 Infection, Hospitalization, and Mortality in Adults With and Without Cancer. JAMA Netw Open. 2023;6(8): e2331617. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamanetworkopen.2023.31617.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Turtle L, Elliot S, Drake TM, Thorpe M, Khoury EG, Greenhalf W, Hardwick HE, Leeming G, Law A, Oosthuyzen W, Pius R, Shaw CA, Baillie JK, Openshaw PJM, Docherty AB, Semple MG, Harrison EM, Palmieri C. Changes in hospital mortality in patients with cancer during the COVID-19 pandemic (ISARIC-CCP-UK): a prospective, multicentre cohort study. Lancet Oncol. 2024;25(5):636–48. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s1470-2045(24)00107-4.

    Article  PubMed  Google Scholar 

  5. Hartman HE, Sun Y, Devasia TP, Chase EC, Jairath NK, Dess RT, Jackson WC, Morris E, Li P, Hochstedler KA, Abbott MR, Kidwell KM, Walter V, Wang M, Wang X, Zaorsky NG, Schipper MJ, Spratt DE. Integrated Survival Estimates for Cancer Treatment Delay Among Adults With Cancer During the COVID-19 Pandemic. JAMA Oncol. 2020;6(12):1881–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamaoncol.2020.5403.

    Article  PubMed  Google Scholar 

  6. Gong IY, Vijenthira A, Powis M, Calzavara A, Patrikar A, Sutradhar R, Hicks LK, Wilton D, Singh S, Krzyzanowska MK, Cheung MC. Association of COVID-19 Vaccination With Breakthrough Infections and Complications in Patients With Cancer. JAMA Oncol. 2023;9(3):386–94. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamaoncol.2022.6815.

    Article  PubMed  Google Scholar 

  7. Au L, Fendler A, Shepherd STC, Rzeniewicz K, Cerrone M, Byrne F, Carlyle E, Edmonds K, Del Rosario L, Shon J, Haynes WA, Ward B, Shum B, Gordon W, Gerard CL, Xie W, Joharatnam-Hogan N, Young K, Pickering L, Furness AJS, Larkin J, Harvey R, Kassiotis G, Gandhi S, Swanton C, Fribbens C, Wilkinson KA, Wilkinson RJ, Lau DK, Banerjee S, Starling N, Chau I, Turajlic S. Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2. Nat Med. 2021;27(8):1362–6. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41591-021-01387-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brest P, Mograbi B, Hofman P, Milano G. COVID-19 vaccination and cancer immunotherapy: should they stick together? Br J Cancer. 2022;126(1):1–3. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41416-021-01618-0.

    Article  CAS  PubMed  Google Scholar 

  9. Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, Davies MJ, Ernstoff MS, Fecher L, Ghosh M, Jaiyesimi I, Mammen JS, Naing A, Nastoupil LJ, Phillips T, Porter LD, Reichner CA, Seigel C, Song JM, Spira A, Suarez-Almazor M, Swami U, Thompson JA, Vikas P, Wang Y, Weber JS, Funchain P, Bollin K. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39(36):4073–126. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/jco.21.01440.

    Article  CAS  PubMed  Google Scholar 

  10. Brahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, Gerber DE, Hamad L, Hansen E, Johnson DB, Lacouture ME, Masters GA, Naidoo J, Nanni M, Perales MA, Puzanov I, Santomasso BD, Shanbhag SP, Sharma R, Skondra D, Sosman JA, Turner M, Ernstoff MS. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/jitc-2021-002435.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, Lyon AR, Wick W, Kostine M, Peters S, Jordan K, Larkin J. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(12):1217–38. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.annonc.2022.10.001.

    Article  CAS  PubMed  Google Scholar 

  12. Xu C, Chen YP, Du XJ, Liu JQ, Huang CL, Chen L, Zhou GQ, Li WF, Mao YP, Hsu C, Liu Q, Lin AH, Tang LL, Sun Y, Ma J. Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ. 2018;363: k4226. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/bmj.k4226.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, Shabafrouz K, Ribi C, Cairoli A, Guex-Crosier Y, Kuntzer T, Michielin O, Peters S, Coukos G, Spertini F, Thompson JA, Obeid M. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563–80. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41571-019-0218-0.

    Article  CAS  PubMed  Google Scholar 

  14. Cook S, Samuel V, Meyers DE, Stukalin I, Litt I, Sangha R, Morris DG, Heng DYC, Pabani A, Dean M, Navani V. Immune-Related Adverse Events and Survival Among Patients With Metastatic NSCLC Treated With Immune Checkpoint Inhibitors. JAMA Netw Open. 2024;7(1): e2352302. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamanetworkopen.2023.52302.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sznol M, Ferrucci PF, Hogg D, Atkins MB, Wolter P, Guidoboni M, Lebbé C, Kirkwood JM, Schachter J, Daniels GA, Hassel J, Cebon J, Gerritsen W, Atkinson V, Thomas L, McCaffrey J, Power D, Walker D, Bhore R, Jiang J, Hodi FS, Wolchok JD. Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma. J Clin Oncol. 2017;35(34):3815–22. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/jco.2016.72.1167.

    Article  CAS  PubMed  Google Scholar 

  16. Rha SY, Oh DY, Yañez P, Bai Y, Ryu MH, Lee J, Rivera F, Alves GV, Garrido M, Shiu KK, Fernández MG, Li J, Lowery MA, Çil T, Cruz FM, Qin S, Luo S, Pan H, Wainberg ZA, Yin L, Bordia S, Bhagia P, Wyrwicz LS. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(11):1181–95. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s1470-2045(23)00515-6.

    Article  CAS  PubMed  Google Scholar 

  17. Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv264–6. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/annonc/mdy162.

    Article  CAS  PubMed  Google Scholar 

  18. Jim HSL, Knoop H, Dicker AP (2021) Immune Checkpoint Inhibitor Therapy Toxicities. In: Jama, vol 326. vol 1. United States, p 87. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jama.2021.6030

  19. Amoroso V, Gallo F, Alberti A, Paloschi D, Ferrari Bravo W, Esposito A, Cosentini D, Grisanti S, Pedersini R, Petrelli F, Berruti A. Immune-related adverse events as potential surrogates of immune checkpoint inhibitors’ efficacy: a systematic review and meta-analysis of randomized studies. ESMO Open. 2023;8(2): 100787. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.esmoop.2023.100787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gougis P, Jochum F, Abbar B, Dumas E, Bihan K, Lebrun-Vignes B, Moslehi J, Spano JP, Laas E, Hotton J, Reyal F, Hamy AS, Salem JE. Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade-a worldwide perspective. EClinicalMedicine. 2024;70: 102536. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.eclinm.2024.102536.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gradone AL, Ma VT, Vasbinder A, Fecher LA, Yentz S, Hayek SS, Lao CD. Increased myositis and possible myocarditis in melanoma patients treated with immune checkpoint inhibitors in the COVID-19 era. Cancer Immunol Immunother. 2024;73(12):259. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00262-024-03803-5.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Li Z, Zhou Z, Zhang N, Tian B, Chen X, Zhao H, Wang H. Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database. Cancer Immunol Immunother. 2024;74(1):25. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00262-024-03858-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tezuka T, Okuzumi S, Nakashima C, Ide T, Imai S, Mitsuboshi S, Kuwahara Y, Takizawa T, Seki M, Minematsu N, Aragane N, Nakahara J, Hori S, Nakane S, Suzuki S. Dysautonomia associated with immune checkpoint inhibitors. J Neurol. 2023;270(7):3413–23. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00415-023-11667-5.

    Article  CAS  PubMed  Google Scholar 

  24. Liu G, Zhang S, Mo Z, Huang T, Yu Q, Lu X, He P. Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database. Front Pharmacol. 2024;15:1407894. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fphar.2024.1407894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bertrand A, Kostine M, Barnetche T, Truchetet ME, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med. 2015;13:211. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12916-015-0455-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Khoja L, Day D, Wei-Wu Chen T, Siu LL, Hansen AR. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol. 2017;28(10):2377–85. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/annonc/mdx286.

    Article  CAS  PubMed  Google Scholar 

  27. Zambelli A, Chiudinelli L, Fotia V, Negrini G, Bosetti T, Callegaro A, Di Croce A, Caremoli ER, Moro C, Milesi L, Poletti P, Tasca C, Mandalà M, Merelli B, Mosconi S, Arnoldi E, Bettini A, Bonomi L, Messina C, Ghilardi L, Chirco A, Maracino M, Tondini C. Prevalence and Clinical Impact of SARS-CoV-2 Silent Carriers Among Actively Treated Patients with Cancer During the COVID-19 Pandemic. Oncologist. 2021;26(4):341–7. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/onco.13654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Candoni A, Petruzzellis G, Sperotto A, Andreotti V, Giavarra M, Corvaja C, Minisini A, Comuzzi C, Tascini C, Fanin R, Fasola G. Detection of SARS-CoV-2 infection prevalence in 860 cancer patients with a combined screening procedure including triage, molecular nasopharyngeal swabs and rapid serological test. A report from the first epidemic wave. PLoS One. 2022;17(2):e0262784. https://doiorg.publicaciones.saludcastillayleon.es/10.1371/journal.pone.0262784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pinato DJ, Patel M, Scotti L, Colomba E, Dolly S, Loizidou A, Chester J, Mukherjee U, Zambelli A, Dalla Pria A, Aguilar-Company J, Bower M, Salazar R, Bertuzzi A, Brunet J, Lambertini M, Tagliamento M, Pous A, Sita-Lumsden A, Srikandarajah K, Colomba J, Pommeret F, Seguí E, Generali D, Grisanti S, Pedrazzoli P, Rizzo G, Libertini M, Moss C, Evans JS, Russell B, Harbeck N, Vincenzi B, Biello F, Bertulli R, Ottaviani D, Liñan R, Rossi S, Carmona-García MC, Tondini C, Fox L, Baggi A, Fotia V, Parisi A, Porzio G, Queirolo P, Cruz CA, Saoudi-Gonzalez N, Felip E, Roqué Lloveras A, Newsom-Davis T, Sharkey R, Roldán E, Reyes R, Zoratto F, Earnshaw I, Ferrante D, Marco-Hernández J, Ruiz-Camps I, Gaidano G, Patriarca A, Bruna R, Sureda A, Martinez-Vila C, Sanchez de Torre A, Berardi R, Giusti R, Mazzoni F, Guida A, Rimassa L, Chiudinelli L, Franchi M, Krengli M, Santoro A, Prat A, Tabernero J, Van Hemelrijck M, Diamantis N, Gennari A, Cortellini A. Time-Dependent COVID-19 Mortality in Patients With Cancer: An Updated Analysis of the OnCovid Registry. JAMA Oncol. 2022;8(1):114–22. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamaoncol.2021.6199.

    Article  PubMed  Google Scholar 

  30. Grivas P, Khaki AR, Wise-Draper TM, French B, Hennessy C, Hsu CY, Shyr Y, Li X, Choueiri TK, Painter CA, Peters S, Rini BI, Thompson MA, Mishra S, Rivera DR, Acoba JD, Abidi MZ, Bakouny Z, Bashir B, Bekaii-Saab T, Berg S, Bernicker EH, Bilen MA, Bindal P, Bishnoi R, Bouganim N, Bowles DW, Cabal A, Caimi PF, Chism DD, Crowell J, Curran C, Desai A, Dixon B, Doroshow DB, Durbin EB, Elkrief A, Farmakiotis D, Fazio A, Fecher LA, Flora DB, Friese CR, Fu J, Gadgeel SM, Galsky MD, Gill DM, Glover MJ, Goyal S, Grover P, Gulati S, Gupta S, Halabi S, Halfdanarson TR, Halmos B, Hausrath DJ, Hawley JE, Hsu E, Huynh-Le M, Hwang C, Jani C, Jayaraj A, Johnson DB, Kasi A, Khan H, Koshkin VS, Kuderer NM, Kwon DH, Lammers PE, Li A, Loaiza-Bonilla A, Low CA, Lustberg MB, Lyman GH, McKay RR, McNair C, Menon H, Mesa RA, Mico V, Mundt D, Nagaraj G, Nakasone ES, Nakayama J, Nizam A, Nock NL, Park C, Patel JM, Patel KG, Peddi P, Pennell NA, Piper-Vallillo AJ, Puc M, Ravindranathan D, Reeves ME, Reuben DY, Rosenstein L, Rosovsky RP, Rubinstein SM, Salazar M, Schmidt AL, Schwartz GK, Shah MR, Shah SA, Shah C, Shaya JA, Singh SRK, Smits M, Stockerl-Goldstein KE, Stover DG, Streckfuss M, Subbiah S, Tachiki L, Tadesse E, Thakkar A, Tucker MD, Verma AK, Vinh DC, Weiss M, Wu JT, Wulff-Burchfield E, Xie Z, Yu PP, Zhang T, Zhou AY, Zhu H, Zubiri L, Shah DP, Warner JL, Lopes G. Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium. Ann Oncol. 2021;32(6):787–800. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.annonc.2021.02.024.

    Article  CAS  PubMed  Google Scholar 

  31. Oosting SF, van der Veldt AAM, GeurtsvanKessel CH, Fehrmann RSN, van Binnendijk RS, Dingemans AC, Smit EF, Hiltermann TJN, den Hartog G, Jalving M, Westphal TT, Bhattacharya A, van der Heiden M, Rimmelzwaan GF, Kvistborg P, Blank CU, Koopmans MPG, Huckriede ALW, van Els C, Rots NY, van Baarle D, Haanen J, de Vries EGE. mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial. Lancet Oncol. 2021;22(12):1681–91. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s1470-2045(21)00574-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gilbert D, Hu J, Medina T, Kessler ER, Lam ET. Safety of COVID-19 vaccines in subjects with solid tumor cancers receiving immune checkpoint inhibitors. Hum Vaccin Immunother. 2023;19(1):2207438. https://doiorg.publicaciones.saludcastillayleon.es/10.1080/21645515.2023.2207438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Widman AJ, Cohen B, Park V, McClure T, Wolchok J, Kamboj M. Immune-Related Adverse Events Among COVID-19-Vaccinated Patients With Cancer Receiving Immune Checkpoint Blockade. J Natl Compr Canc Netw. 2022;20(10):1134–8. https://doiorg.publicaciones.saludcastillayleon.es/10.6004/jnccn.2022.7048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Strobel SB, Machiraju D, Kälber KA, Hassel JC. Immune-related adverse events of COVID-19 vaccination in skin cancer patients receiving immune-checkpoint inhibitor treatment. Cancer Immunol Immunother. 2022;71(8):2051–6. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00262-021-03133-w.

    Article  CAS  PubMed  Google Scholar 

  35. Ruiz JI, Lopez-Olivo MA, Geng Y, Suarez-Almazor ME. COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis. J Immunother Cancer. 2023;11(2):e006246. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/jitc-2022-006246.

    Article  PubMed  Google Scholar 

  36. Waissengrin B, Agbarya A, Safadi E, Padova H, Wolf I. Short-term safety of the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors. Lancet Oncol. 2021;22(5):581–3. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s1470-2045(21)00155-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Retnakumar SV, Chauvin C, Bayry J. The implication of anti-PD-1 therapy in cancer patients for the vaccination against viral and other infectious diseases. Pharmacol Ther. 2023;245: 108399. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.pharmthera.2023.108399.

    Article  CAS  PubMed  Google Scholar 

  38. Watson RA, Ye W, Taylor CA, Jungkurth E, Cooper R, Tong O, James T, Shine B, Hofer M, Jenkins D, Pell R, Ieremia E, Jones S, Maldonado-Perez D, Roberts ISD, Coupe N, Middleton MR, Payne MJ, Fairfax BP. Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination. J Immunother Cancer. 2024;12(4):e008151. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/jitc-2023-008151.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sumi T, Koshino Y, Michimata H, Nagayama D, Watanabe H, Yamada Y, Chiba H (2022) Cytokine release syndrome in a patient with non-small cell lung cancer on ipilimumab and nivolumab maintenance therapy after vaccination with the mRNA-1273 vaccine: a case report. In: Transl Lung Cancer Res. 2022;11(9). Translational Lung Cancer Research. All rights reserved., China, pp 1973–1976. https://doiorg.publicaciones.saludcastillayleon.es/10.21037/tlcr-22-388

  40. Lasagna A, Lenti MV, Cassaniti I, Sacchi P. Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report. Immunotherapy. 2022;14(12):915–25. https://doiorg.publicaciones.saludcastillayleon.es/10.2217/imt-2021-0342.

    Article  CAS  PubMed  Google Scholar 

  41. Makiguchi T, Fukushima T, Tanaka H, Taima K, Takayasu S, Tasaka S (2022) Diabetic ketoacidosis shortly after COVID-19 vaccination in a non-small-cell lung cancer patient receiving combination of PD-1 and CTLA-4 inhibitors: A case report. In: Thorac Cancer, vol 13. vol 8. © 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd., Singapore, pp 1220–1223. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/1759-7714.14352

  42. Mieczkowska K, Kaubisch A, McLellan BN (2021) Exacerbation of psoriasis following COVID-19 vaccination in a patient previously treated with PD-1 inhibitor. In: Dermatol Ther, vol 34. vol 5. United States, p e15055. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/dth.15055

  43. Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, Grinberg T, Auster O, Dagan N, Balicer RD, Kornowski R. Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. N Engl J Med. 2021;385(23):2132–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1056/NEJMoa2110737.

    Article  CAS  PubMed  Google Scholar 

  44. Karam R, Iskandar K, Watfa M, Zeitoun A. Serious adverse events following immunization with COVID-19 vaccines in Lebanon: a retrospective analysis of the National Pharmacovigilance Database. BMC Public Health. 2024;24(1):2905. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12889-024-20297-z.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ochoa S, Abers MS, Rosen LB, Rump A, Howe K, Lieberman JA, Wright BL, Suez D, Krausz M, Grimbacher B, Lionakis MS, Uzel G. Management and outcome of COVID-19 in CTLA-4 insufficiency. Blood Adv. 2023;7(19):5743–51. https://doiorg.publicaciones.saludcastillayleon.es/10.1182/bloodadvances.2023010105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lin A, Qi C, Wei T, Li M, Cheng Q, Liu Z, Luo P, Zhang J. CAMOIP: a web server for comprehensive analysis on multi-omics of immunotherapy in pan-cancer. Brief Bioinform. 2022;23(3):bbac129. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/bib/bbac129.

    Article  CAS  PubMed  Google Scholar 

  47. Liu Z, Han L, Ji X, Wang X, Jian J, Zhai Y, Xu Y, Wang F, Ning F. Multi-omics analysis and experiments uncover the function of cancer stemness in ovarian cancer and establish a machine learning-based model for predicting immunotherapy responses. Front Immunol. 2024;15:1486652. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fimmu.2024.1486652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Saga University Hospital, 5-1-1 Nabeshima, Saga City, Saga, 849-8501, Japan

    Sakiko Kimura, Rintaro Sogawa, Tatsuya Furuno & Chisato Shimanoe

  2. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Hiroo Katsuya, Chiho Nakashima, Naoko Sueoka-Aragane & Shinya Kimura

  3. Department of Medical Information, Saga University Hospital, Saga City, Saga, Japan

    Koji Hayashida

  4. Cancer Center, Saga University Hospital, Saga City, Saga, Japan

    Kazumi Sasaki

  5. Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Moriyasu Yamauchi & Yoichiro Sugiyama

  6. Department of Surgery, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Hirokazu Noshiro

  7. Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Motohiro Esaki

  8. Department of Urology, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Mitsuru Noguchi

  9. Liver Center, Faculty of Medicine, Saga University Hospital, Saga University, Saga City, Saga, Japan

    Hirokazu Takahashi

  10. Division of Metabolism and Endocrinology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Keizo Anzai

  11. Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Masatoshi Yokoyama

  12. Division of Dermatology, Department Of Internal Medicine, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Kazunari Sugita

  13. Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Yoshio Yamashita

  14. Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga City, Saga, Japan

    Atsushi Kawaguchi

Authors
  1. Sakiko Kimura
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Hiroo Katsuya
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Chiho Nakashima
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Naoko Sueoka-Aragane
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Koji Hayashida
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Kazumi Sasaki
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Rintaro Sogawa
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Tatsuya Furuno
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Moriyasu Yamauchi
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Yoichiro Sugiyama
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Hirokazu Noshiro
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Motohiro Esaki
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Mitsuru Noguchi
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Hirokazu Takahashi
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Keizo Anzai
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Masatoshi Yokoyama
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Kazunari Sugita
    View author publications

    You can also search for this author inPubMed Google Scholar

  18. Yoshio Yamashita
    View author publications

    You can also search for this author inPubMed Google Scholar

  19. Atsushi Kawaguchi
    View author publications

    You can also search for this author inPubMed Google Scholar

  20. Shinya Kimura
    View author publications

    You can also search for this author inPubMed Google Scholar

  21. Chisato Shimanoe
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Sakiko K, HK, Shinya K and CS made substantial contributions to study conception, design, analysis, and data interpretation. CN, NA, KH, KS, RS, TF, MY, YS, HN, ME, MN, HT, KA, MY, KS and YY enrolled patients and collected data. AK performed statistical analysis. Sakiko K and HK wrote the paper. Shinya K and CS critically reviewed the drafts, and all authors approved the final version.

Corresponding author

Correspondence to Sakiko Kimura.

Ethics declarations

Ethics approval and consent to participate

The present study was approved by the Clinical Research Ethics Review Committee of Saga University Hospital (Saga University Clinical Research Review Board; Approval No.: 2023-12-02), and conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki. The need for informed consent was waived owing to the retrospective nature of the study. The official website of our institution was used to allow patients to opt out from participation.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kimura, S., Katsuya, H., Nakashima, C. et al. Incidence of severe adverse events in cancer patients after treatment with immune-checkpoint inhibitors during the COVID- 19 pandemic. BMC Immunol 26, 33 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12865-025-00711-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12865-025-00711-w

Keywords

BMC Immunology

ISSN: 1471-2172

Contact us