Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer.

Tumor proportion score (TPS) and combined positive score ([CPS] includes immune cells), 2 methods for scoring programmed death ligand 1 (PD-L1) expression, have been used in clinical trials investigating the immune checkpoint inhibitor pembrolizumab in head and neck squamous cell carcinoma (HNSCC). These trials resulted in regulatory approval for pembrolizumab in the first- and second-line setting outside the United States. We performed a post hoc analysis of the KEYNOTE-040 study (NCT02252042) to determine whether CPS is a practical and suitable alternative scoring method to TPS. In KEYNOTE-040, patients with metastatic HNSCC received pembrolizumab or investigator choice of standard of care (SOC). The relative utility and equivalence of CPS ≥ 50 and TPS ≥ 50% for defining PD-L1 expression status in patients with HNSCC and comparability of scoring methods by tandem receiver operating characteristic (ROC) analysis were analyzed. The cutoff for each method was also evaluated. CPS ≥ 50 appeared equivalent to TPS ≥ 50% for predicting objective response rate (ORR), overall survival, and progression-free survival. ORR for pembrolizumab versus SOC was 26.2 versus 8.5% for TPS ≥ 50%, 28.1 versus 7.7% for CPS ≥ 50, 10.6 versus 11.6% for TPS < 50%, and 10.0 versus 12.0% for CPS < 50. Tandem ROC analysis showed that TPS 50% and CPS 50 maximized delta Youden index and suggested that CPS is more sensitive than TPS at lower cutoffs (i.e., CPS ≥ 1). In conclusion, CPS 50 can be used interchangeably with TPS 50% to determine PD-L1 status in patients with HNSCC. CPS may be more sensitive than TPS at lower cutoffs.

Performance evaluation of the ADVIA Centaur anti-HBe and HBeAg assays.

BACKGROUND: Detection of HBeAg and anti-HBe is valuable for the evaluation and therapeutic management of hepatitis B infection. OBJECTIVES: To determine the clinical performance of the newly CE-approved(a) HBeAg and anti-HBe assays on the fully automated, random access ADVIA Centaur immunoassay system. STUDY DESIGN: Patient samples collected at two sites were used to compare the ADVIA Centaur assays to Abbott AxSYM assays. Consensus of discordant results was reached using Roche Elecsys assays. Additionally, two well-characterized seroconversion panels were evaluated. RESULTS: The ADVIA Centaur HBeAg assay sensitivity was 100% and specificity was 99.5%. The ADVIA Centaur anti-HBe assay sensitivity was 100% and the resolved specificity was 98.2%. Fewer samples required retesting with the ADVIA Centaur assays than with the AxSYM. In two well-characterized seroconversion panels, the ADVIA Centaur anti-HBe assay detected anti-HBe 20-25 days earlier than the AxSYM assay; the ADVIA Centaur and AxSYM HBeAg assays detected HBe reactivity on the same day. CONCLUSIONS: The ADVIA Centaur HBeAg and anti-HBe assays demonstrated good sensitivity and specificity, and thus are suitable for clinical use. Their novel algorithms require reduced retesting, suggesting these assays may be more cost effective.

Evaluation of the IMMULITE® 2000 CMV IgM assay.

BACKGROUND: Diagnosis of cytomegalovirus (CMV) infection is challenging because of the high rate of asymptomatic infection and the low specificity of associated symptoms and signs. As a result, laboratory testing is an essential aid in making an accurate diagnosis. The presence of CMV IgM is indicative of primary CMV infection. In pregnancy, diagnosis of primary infection is important because primary maternal infection increases fetal infection risk substantially. Fetal infection can result in serious sequelae ranging from neurological deficits to death. Diagnosis among the immunocompromised is also critical for the timely initiation of therapy that can reduce morbidity and mortality risk. METHODS: The IMMULITE® 2000 CMV IgM assay qualitatively detects CMV IgM antibodies in human serum or plasma to aid in the diagnosis of current or recent CMV infection. To determine expected values in apparently healthy subjects, 136 samples were tested. Reproducibility, normal range, and method comparison studies were also performed to evaluate the assay's performance. The assay's reproducibility was evaluated across three sites. Seven hundred and eighteen (n = 718) individual patient serum samples, which included samples from CMV IgM-positive (n = 109, determined by the Abbott IMx CMV or the Diamedix CMV IgM assays), pregnant (n = 210), HIV-positive (n = 30), immunosuppressed (n = 102), and transplant patients (n = 17) and from patients with potentially cross-reacting conditions (n = 136) were evaluated in the method comparison study. The positive, negative, and overall agreement between the IMMULITE 2000 CMV IgM assay and the VIDAS CMV IgM assay (predicate assay) were determined. RESULTS: The assay demonstrated excellent reproducibility with a total CV of less than 10%. The positive, negative, and overall agreement between the IMMULITE 2000 assay and the VIDAS assay were > 95% for the method comparison samples. Among potentially cross-reactive samples, the overall agreement between the two assays was 96%. Similarly, among the immunocompromised and pregnant subjects, the overall agreement was ~96% and ~97%, respectively. CONCLUSIONS: The IMMULITE 2000 CMV IgM assay demonstrated excellent reproducibility, minimal cross-reactivity, and performance comparable to that of the VIDAS CMV IgM assay. It can aid in the diagnosis of acute CMV or recent CMV infection by qualitatively detecting the CMV IgM antibodies in human serum or plasma.

Performance evaluation of the ADVIA Centaur(®) HIV Ag/Ab Combo assay.

Early diagnosis of HIV infection and appropriate care reduces morbidity and mortality. As a result, recent guidelines recommend that HIV screening be routinely included in patient care. Routine screening will likely result in more patients being tested prior to seroconversion; fourth-generation assays can facilitate diagnosis in these patients. This study evaluated the performance of the automated fourth-generation ADVIA Centaur(®) HIV Ag/Ab Combo assay. Samples from three sites were tested using the HIV Ag/Ab Combo assay and a CE-marked predicate assay. The HIV Ag/Ab Combo assay's relative sensitivity was 98.36% (599/609; 95% confidence interval: 97.00-99.21%), and the relative specificity was 99.74% (7743/7763; 95% confidence interval: 99.60-99.84%). The HIV Ag/Ab Combo assay detected seroconversion at the same bleed or at least one bleed earlier in 34/37 panels compared to the CE-marked predicate assay. Compared to the final result, the HIV Ag/Ab Combo assay's sensitivity was 100% (598/598; 95% confidence interval: 99.39-100.00%), and the specificity was 99.74% (7753/7773; 95% confidence interval: 99.60-99.84%). Sensitivity was 100% for the HIV genotypes tested. The HIV Ag/Ab Combo assay is a sensitive and specific assay that can assist clinicians in the early diagnosis of HIV infection.