Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer

Abstract

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan–Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4–16.7] vs. 21.03 [95% CI: 14.7–24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26–8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72–19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

Diagnosis of opportunistic infections in non-small cell lung cancer

“…Несомненно, для достоверных выводов необходимы дальнейшие исследования с включением большего числа пациентов. Полученные данные коррелируют с результатами мировых исследований по проблемам ОИ у онкологических больных [4,[9][10][11]. В частности, опубликованы данные о развитии у больных НМРЛ, получающих противоопухолевое лечение, ОИ, этиологическими агентами которых были ЦМВ, Pneumocystis jirovecii и другие микроорганизмы [12].…”

Antibiotic treatment and survival in non-small cell lung cancer patients receiving immunotherapy: a systematic review and meta-analysis

“…Among the other understudied clinical factors that deserve future research are the fact that patients may experience delays in their cancer treatment due to infection, which may contribute to poorer survival, the lack of information on the outcome of the infection following the antibiotic treatment, the type of changes in microbiota associated with survival, the lack of information on cancer-specific survival ( 47 ). All of these are important considerations for future research studies.…”