Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: a real-world study

Abstract

Anti-COVID-19 vaccination may have functional implications for immune checkpoint inhibitor treatment in patients with cancer. This study was undertaken to determine whether the safety or efficacy of anti-PD-1 therapy is reduced in patients with cancer during COVID-19 vaccination. A large multicenter observational study was conducted in 83 Chinese hospitals between January 28, 2021 and September 30, 2021. A total of 3552 patients were screened and 2048 eligible patients with cancer receiving PD-1 inhibitor treatment were recruited. All enrolled patients had received camrelizumab treatment alone or in conjunction with other cancer therapies. Among these, 1518 (74.1%) patients received the BBIBP-CorV vaccine and were defined as the vaccinated subgroup. The remaining 530 (25.9%) patients did not receive anti-COVID-19 vaccination and were defined as the non-vaccinated subgroup. For all participants, Response Evaluation Criteria in Solid Tumor and Common Terminology Criteria for Adverse Events criteria were used to evaluate the efficacy and safety of camrelizumab treatment, respectively. Propensity score match analysis with the optimal pair matching was used to compare these criteria between the vaccinated and non-vaccinated subgroups. A total of 2048 eligible patients with cancer were included (median age 59 years, 27.6% female). Most patients (98.8%) had metastatic cancer of the lung, liver or intestinal tract. Aside from the PD-1 inhibitor treatment, 55.9% of patients received additional cancer therapies. 1518 (74.1%) patients received the BBIBP-CorV vaccine with only mild side effects reported. The remaining patients did not receive COVID-19 vaccination and had a statistically greater percentage of comorbidities. After matching for age, gender, cancer stage/types, comorbidity and performance status, 1060 patients (530 pairs) were selected for propensity score match analysis. This analysis showed no significant differences in overall response rate (25.3% vs 28.9%, p=0.213) and disease control rate (64.6% vs 67.0%, p=0.437) between vaccinated and non-vaccinated subgroups. Immune-related adverse events (irAEs) were reported in both subgroups after camrelizumab treatment. Among vaccinated patients who experienced irAEs, the median interval between the first dose of camrelizumab treatment and the first vaccine shot was ≤16 days. Compared with the non-vaccinated subgroup, irAEs in vaccinated patients were more frequently reported as mild (grade 1 or 2 irAEs; 33.8% vs 19.8%, p<0.001) and these patients were less likely to discontinue the PD-1 inhibitor treatment (4.2% vs 20.4%, p<0.001). Severe irAEs (grade 3 irAE or higher) related to camrelizumab treatment were reported, however no significant differences in the frequency of such events were observed between the vaccinated and non-vaccinated subgroups. The COVID-19 vaccine, BBIBP-CorV, did not increase severe anti-PD-1-related adverse events nor did it reduce the clinical efficacy of camrelizumab in patients with cancer. Thus, we conclude that patients with cancer need not suspend anti-PD-1 treatment during COVID-19 vaccination.

Cancer Patients and the COVID-19 Vaccines: Considerations and Challenges

“…Mei et al, speculated that giving the COVID-19 vaccine and anti-PD1 therapy within close temporal proximity of each other may enhance co-stimulatory and reduce co-inhibitory regulation, accounting for the increase in mild AEs in vaccinated patients. Additionally, they also speculated that this increase in immune response allows for the chemotherapy to work more effectively, consistent with their finding of vaccinated patients having higher disease control rates [ 66 ].…”

“…Mei et al, compared 1518 vaccinated cancer patients (288 with one dose, 1134 with two doses, 96 with three doses) receiving camrelizumab alone or in conjunction with other therapies to unvaccinated patients. Compared with matched unvaccinated patients, a statistically greater percentage of vaccinated patients had mild AE ≤ 2 (33.8% vs. 19.8%; p < 0.001) following camrelizumab treatment [ 66 ].…”

Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course

“…A recently published multicenter observational study included 2048 patients who had previously received anti-PD-1 therapy and were divided into vaccinated subgroup (receiving inactivated SARS-CoV-2 virus vaccine) and non-vaccinated subgroup for comparison. Both subgroups were similar in terms of ICIs efficacy, while in terms of safety, the vaccinated subgroup was more likely to have mild irAE, while the incidence of severe irAE was instead reduced ( 167 ). Although case of cytokine release syndrome occurring 5 days after BTN162b2 mRNA COVID-19 vaccination in patient with long-term anti-PD-1 therapy have been reported ( 168 ), the benefit-risk profile still strongly supports vaccination in cancer patients.…”

Potentially improved response of COVID-19 vaccinated nasopharyngeal cancer patients to combination therapy with anti-PD-1 blockade and chemotherapy

“…Anti-PD-1 treatment was demonstrated to be effective in nasopharyngeal cancer (NPC) patients 1 . During the COVID-19 pandemic, concern was raised whether anti-PD-1 treatment can interfere with COVID-19 vaccination in NPC patients, although our previous study showed that the efficacy and safety of anti-PD-1 treatment was not reduced in general cancer patients vaccinated with SinoVac 2 . NPC affects the upper respiratory tract, where the COVID-19 infection takes place.…”