Retrospective study evaluating immune-related adverse events in cancer patients treated with pembrolizumab.

INTRODUCTION: Pembrolizumab has been on the market for several years, but most of the safety data is based on clinical trials with limited literature evaluating post-marketing immune-related adverse events (irAEs) associated with its use. This study aimed to evaluate the characteristics of irAEs associated with pembrolizumab. METHODS: We included adult patients who had received pembrolizumab between January 2016 and December 2020. The patient electronic profiles and the pharmacy adverse event reporting system were reviewed to identify adverse events. Patients were followed from the start of treatment until 12 months after the last dose, end of the study, or death. The characteristics of the patients and the irAEs were recorded. Univariate and multivariate logistic regression analyses were performed to identify variables associated with the development of irAE. RESULTS: During the study period, 223 patients and 1601 cycles of pembrolizumab were evaluated. A total of 67 irAEs were reported in 58 patients. The median age was 53 years (range 18-84), and most patients were males (75%) with metastatic lung cancer (62%). The most common irAEs were respiratory (30%), followed by gastrointestinal (25%), endocrine (24%), and dermatologic (21%). Among the reported irAEs, 28 were associated with hospital admission, 15 required long-term treatment, and 9 resulted in pembrolizumab discontinuation. In logistic regression, there were no significant predictors associated with irAE. CONCLUSIONS: Respiratory irAEs were the most common in our population. We were unable to identify predictors of irAE in this cohort. Further studies are necessary to identify predictors of adverse events.

Validation of the CSRFENCE score for prediction of febrile neutropenia during chemotherapy cycles 2-6.

PURPOSE: Though febrile neutropenia (FN) risk prediction models are important in clinical practice, their external validation is limited. In this study, we validated the Cycle-Specific Risk of FEbrile Neutropenia after ChEmotherapy (CSRFENCE) score for predicting FN. METHODS: We reviewed the medical records of patients with solid malignancies and diffuse large B-cell lymphoma during chemotherapy cycles 2-6 and recorded if patients developed FN, defined as absolute neutrophil counts less than 500 cells/microL with fever more than or equal to 38.2 â„ƒ. The CSRFENCE score was determined by adding the risk factors' coefficients described by the original study; subsequently, the score was used to classify chemotherapy cycles into the following risk groups for developing FN: low, intermediate, high, and very high risk. The discriminatory ability of the score was assessed using area under the receiver operating characteristics curve (AUROCC) and incidence rate ratios (IRR) within each CSRFENCE risk group. RESULTS: We analyzed 2870 chemotherapy cycles, of which 42 (1.5%) were associated with FN. Among those, 3 (7.1%), 14 (33.3%), 5 (12%), and 20 (47.6%) were classified as low, intermediate, high, and very high risk for developing FN, respectively. The AUROCC was 0.72 (95% CI 0.64-0.81). Compared with the low risk group (n = 666), the IRR of developing FN was 1.01 (95% CI 0.15-43.37), 0.69 (95% CI 0.08-32.46) and 1.17 (95% CI 0.17-49.49) in the intermediate (n = 1431), high (n = 498) and very high (n = 275) risk groups, respectively. CONCLUSION: The CSRFENCE model can moderately stratify patients into four risk groups for predicting FN prior to chemotherapy cycles 2-6.

Validation of the FENCE Risk Groups for Prediction of Febrile Neutropenia With First-Cycle Chemotherapy.

BACKGROUND: The FEbrile Neutropenia after ChEmotherapy (FENCE) score was developed to estimate the risk of febrile neutropenia (FN) at first cycle of chemotherapy but has not been externally validated. We aimed to validate the FENCE score based on its risk groups in patients treated at a comprehensive cancer center. METHODS: We conducted a retrospective study of treatment-naïve adult patients with solid tumors and diffuse large B-cell lymphoma who received first-cycle chemotherapy between January and November 2019. Patients were followed until the second cycle of chemotherapy to identify any FN events (neutrophil count <0.5 × 109/L with fever ≥38.2°C). The FENCE score was determined and patients classified as low, intermediate, high, and very high risk. The discriminatory ability of classifying patients into FENCE risk groups was calculated as the area under the receiver operating characteristics curve and incidence rate ratios within each FENCE risk group. RESULTS: FN was documented during the first cycle of chemotherapy in 45 of the 918 patients included (5%). The area under the receiver operating characteristics curve was 0.66 (95% confidence interval [CI] = 0.58 to 0.73). Compared with the low-risk group (n = 285), the incidence rate ratio of developing FN was 1.58 (95% CI = 0.54 to 5.21), 3.16 (95% CI = 1.09 to 10.25), and 3.93 (95% CI = 1.46 to 12.27) in the intermediate (n = 293), high (n = 162), and very high (n = 178) risk groups, respectively. CONCLUSIONS: In this study, classifying patients into FENCE risk groups demonstrated moderate discriminatory ability for predicting FN. Further validation in multicenter studies is necessary to determine its generalizability.