Immune checkpoint blocking impact and nomogram prediction of COVID-19 inactivated vaccine seroconversion in patients with cancer: a propensity-score matched analysis

Abstract

BackgroundPatients with cancer on active immune checkpoint inhibitors therapy were recommended to seek prophylaxis from COVID-19 by vaccination. There have been few reports to date to discuss the impact of progression cell death-1 blockers (PD-1B) on immune or vaccine-related outcomes, and what risk factors that contribute to the serological status remains to be elucidated. The study aims to find the impact of PD-1B on vaccination outcome and investigate other potential risk factors associated with the risk of seroconversion failure.MethodsPatients with active cancer treatment were retrospectively enrolled to investigate the interaction effects between PD-1B and vaccination. Through propensity score matching of demographic and clinical features, the seroconversion rates and immune/vaccination-related adverse events (irAE and vrAE) were compared in a head-to-head manner. Then, a nomogram predicting the failure risk was developed with variables significant in multivariate regression analysis and validated in an independent cohort.ResultsPatients (n=454) receiving either PD-1B or COVID-19 vaccination, or both, were matched into three cohorts (vac+/PD-1B+, vac+/PD-1B-, and vac-/PD-1B+, respectively), with a non-concer control group of 206 participants. 68.1% (94/138), 71.3% (117/164), and 80.5% (166/206) were seropositive in vac+/PD-1B+cohort, vac+/PD-1B- cohort, and non-cancer control group, respectively. None of irAE or vrAE was observed to be escalated in PD-1B treatment except for low-grade rash.The vaccinated patients with cancer had a significantly lower rate of seroconversion rates than healthy control. A nomogram was thus built that encompassed age, pathology, and chemotherapy status to predict the seroconversion failure risk, which was validated in an independent cancer cohort of 196 patients.ConclusionAlthough patients with cancer had a generally decreased rate of seroconversion as compared with the healthy population, the COVID-19 vaccine was generally well tolerated, and seroconversion was not affected in patients receiving PD-1B. A nomogram predicting failure risk was developed, including age, chemotherapy status, pathology types, and rheumatic comorbidity.

Efficacy of mRNA anti-SARS-CoV-2 vaccination and dynamics of humoral immune response in patients with solid tumors: results from the institutional registry of an Italian tertiary cancer center

“… 18 – 22 In the subset of patients treated with biological therapies, patients treated with PARP inhibitors showed the lowest median value of anti-SARS-CoV-2 IgG levels, in line with the evidence that PARP deficiency may impair peripheral B-cell homeostasis and humoral response. 23 Interestingly, even if immunotherapy does not seem to affect the rate of seroconversion in cancer patients as previously reported, 24 , 25 the more pronounced decrease in antibody levels in the late timepoint that we observed in patients receiving immune checkpoint inhibitors was consistent with two other reports about sustained antibody levels in cancer patients receiving immunotherapy-based treatments at the time of vaccination. 26 , 27 A possible explanation is that immune checkpoint inhibitors may have a positive acute effect, favoring a higher peak of antibody levels soon after the second dose, thus exaggerating the decrease in antibodies at late timepoints.…”

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study

“…Several studies have reported that ICIs do not decrease the immunogenicity of COVID-19 vaccines. 23,31 Notably, the adjusted ORs for seroprotection in patients receiving ICIs were 0.73 (0.11-4.99) for ≥1,084 U/mL on Architect and 0.54 (95% CI 0.07-3.83) for ≥150 U/mL on Elecsys after the second vaccination, which did not decrease as compared with that in All rights reserved. No reuse allowed without permission.…”

COVID-19 Vaccination in Patients With Malignancy; A Systematic Review and Meta-Analysis of the Efficacy and Safety

“…In addition to the type of malignancy and anticancer treatment, patient’s demographic factors such as age and gender might also contribute to the rate of seroconversion in response to vaccination against COVID-19. Ma et al have shown that age is the most prominent predicting factor with regards to the failure of anti-COVID-19 vaccine in cancer patients and negatively correlates with seroconversion rate in these individuals ( 59 ). These results are consistent with another study on BNT162b2 vaccine which shows a remarkable difference between the seroconversion rate of young, versus elderly cancer patients, with the titer levels also being significantly different ( 32 ).…”