Predictors of poor serologic response to COVID-19 vaccine in patients with cancer: a systematic review and meta-analysis

Highlights

• We assessed factors predicting seroconversion of COVID-19 vaccines in patients with cancer.

• Twenty cohort studies with 5,499 patients with cancer were included in the current meta-analysis.

• IGHV mutation status and high levels of IgG/M/A are correlated with seropositivity.

• Chemotherapy and recent 1-year anti-CD20 therapy are correlated with seronegativity.

• Targeted treatment/immunotherapy/endocrine treatment does not affect seroconversion.

Abstract

Backgrounds

Patients with cancer presented a lower probability to obtain seroconversion after a complete course of COVID-19 vaccination. However, little was known on the factors that predict poor seroconversion in this frail population.

Methods

We searched the PubMed, EMBASE, and China National Knowledge Infrastructure databases for all articles within a range of published years from 2019 to 2022 on the predictors of response to COVID-19 vaccine in patients with cancer (last search was updated on 2st March 2022). The odds ratio corresponding to the 95% confidence interval was used to assess the outcome. The statistical heterogeneity among studies was assessed with the Q-test and I² statistics. The review was registered with PROSPERO (CRD42022315687) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

Twenty cohort studies met the inclusion criteria for this study, with 5,499 patients with cancer. We found that advanced age, male patients, and metastatic disease increased negative seropositivity to COVID-19 vaccine. Immunoglobulin heavy chain variable mutation status, high concentration of Ig G, Ig M, and Ig A were correlated with seropositivity. Relating to cancer treatment strategy, anti-CD20 therapy within recent 12 months and chemotherapy were negatively correlated with seroconversion. Meta-analysis found no significant difference associated with targeted treatment, immunotherapy, and endocrine treatment.

Conclusions

Our meta-analysis assessed the factors that predict poor seroconversion in order to plan better prevention strategies in this frail population. The results proposed that enhanced vaccination strategies would be beneficial for the special patients such as advanced male, or patients receiving active chemotherapy, and carefully prevention should be emphasised even after a complete course of vaccination.

Introduction

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world, afflicting more than 459.7 million people, resulting in more than 6 million deaths globally as of 16 March 2022, and with a mortality rate about 1.3%. The morbidity and mortality of COVID-19 were found higher in patients with cancer [1,2]. Worldwide, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths occurred in 2020, and the global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020 [3]. It is precisely because that patients with cancer are purported to have poor COVID-19 outcomes [[4], [5], [6], [7]], and recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against COVID-19 infection [[8], [9], [10]], disease prevention is the most effective way to contain new cases, and major medical societies fostered priority mass vaccination in this high-risk population [11,12].

For this reason, healthcare authorities should prioritise vaccinations for patients with cancer. On the basis of the clinical trials [13], considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. However, researches [[14], [15], [16], [17]] demonstrate a lower probability to obtain seroconversion after a complete course of COVID-19 vaccination, with about 6% of patients with cancer in treatment failed to develop an immune response after mRNA vaccination, as compared to only 0.2% in controls, accounting for a 30-fold higher probability [14].

Patients with cancer have an impaired immune response to COVID-19 vaccination with lower and/or lagged seroconversion rate [18,19]. The vaccination against COVID in cancer (VOICE) study aimed to reveal influences of anti-cancer treatments in response to vaccination [20], and the COVID-19 antiviral response (CAPTURE), a pan-tumour immune monitoring study, suggested a fundamental understanding of the interaction between host immunity, the virus, cancer, and anti-cancer treatments placed in the wider healthcare context in order to minimise harm and optimise cancer outcomes [21]. To propose a tailored approach to COVID-19 vaccination for patients with cancer, a thorough understanding of factors affecting on COVID-19 vaccination efficacy in patients with cancer with poor immune conditions is requisite. We conducted this meta-analysis to assess the factors that predict poor seroconversion comprehensively in order to plan better prevention strategies in this frail population.