Janssen (United States)

Background/Objectives: Ciltacabtagene autoleucel (cilta-cel) for relapsed/refractory multiple myeloma is typically administered inpatient (IP) to monitor for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Because cilta-cel toxicities are typically delayed, outpatient (OP) administration (infusion and early monitoring) is being explored. We synthesized available evidence on OP and IP administration. Methods: MEDLINE, Embase, and Cochrane Library were searched from inception to 5 August 2025, supplemented by conference and gray literature searches. Eligible studies of adults with multiple myeloma receiving cilta-cel reported efficacy, safety, resource use, costs, and/or quality-of-life outcomes; findings were synthesized descriptively due to heterogeneity. Results: Seventy-four records (56 studies) were included; 90 patients received OP cilta-cel. OP clinical evidence (primarily three real-world studies) showed high response rates (ORR: 95%; median follow-up 4.6 months) and reported 1-year PFS and OS of 86% and 96%. In IP studies, median ORR was 91%, with median 1-year PFS 76% and median 1-year OS 85%. Any-grade CRS and ICANS occurred in 79-84% and 17-22% of OP patients (largely low grade); IP cohorts reported a median ICANS incidence of 17% (range 5-23%). Most OP patients were later hospitalized (86-93%), but stays were shorter (median 4-6.5 days) than in an IP cohort (median 19 days). Comparisons were unadjusted and may reflect selection differences. One modeling-based economic analysis estimated savings of ~$19,000 per OP-treated patient. Conclusions: OP cilta-cel appears feasible for selected patients and may reduce costs without compromising outcomes. Findings are descriptive and hypothesis-generating and prospective multicenter studies are needed to define long-term safety, durability, quality of life, and cost-effectiveness.

Successful fibroblast growth factor receptor alterations (FGFRalt) testing is essential for identifying patients eligible for erdafitinib. This analysis of the global ANNAR biomarker study assessed the proportion of valid fibroblast growth factor receptor (FGFR) test results, reasons for test failure, and proportion of FGFRalt in locally advanced/metastatic urothelial cancer (mUC) and non-muscle-invasive bladder cancer (NMIBC). Archival tumor tissue was tested using the QIAGEN therascreen FGFR real-time polymerase chain reaction kit, an approved companion diagnostic for erdafitinib. A total of 2706 mUC and 962 NMIBC samples were tested. The proportion of valid test results was significantly different between mUC and NMIBC (86% and 66%, respectively; p<0.001), which declined with older archival sample age for both mUC (<1yr 89% and ≥3yr 77%; p<0.001) and NMIBC (<1yr 72% and ≥3yr 43%; p<0.001). For mUC, the proportion of valid test results was higher for the primary tumor than for metastatic samples (92% and 55%, respectively; p<0.001) but similar between upper and lower tract disease (87% and 86%, respectively; p=0.7). Common reasons for test failure were low tumor content and insufficient RNA. FGFRalt were found in 19% of mUC (83% mutations; 15% fusions) and 53% of NMIBC (92% mutations; 6.3% fusions) samples. Limitations include the lack of data on sample collection method. This is the first and largest report on factors affecting FGFR test results. To ensure valid FGFR test results, adequate tumor sample amount, RNA quality, short archival sample age, and primary tumor samples are important factors.

BackgroundVOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) demonstrated that antiplatelet therapy with rivaroxaban 2.5 mg twice daily compared with placebo reduced the first event in a composite end point in patients with peripheral artery disease after revascularization. The purpose of this analysis was to (1) evaluate whether rivaroxaban decreased the most severe events and (2) compare the harm and benefit of rivaroxaban on the same scale.MethodsTwo exploratory, hierarchical analyses of the primary efficacy composite outcome and one exploratory analysis of the net clinical benefit composite outcome were prespecified. The global rank method and the win ratio method ranked components of the composite outcome by clinical importance. The net clinical benefit included both efficacy and safety outcomes.ResultsThe global rank method demonstrated that participants on rivaroxaban had fewer or later events than their placebo counterparts when events were compared in a hierarchical manner (primary ranking, P=0.0158). The win ratio approach demonstrated fewer or later fatal and nonfatal ischemic events in the rivaroxaban arm (win ratio, 1.16 [95% CI, 1.03–1.30]; P=0.0167). The net clinical benefit analysis revealed an overall beneficial effect of rivaroxaban when different efficacy and safety end points were included (P<0.001).ConclusionsEvaluation of the VOYAGER PAD primary outcome exploring ranking of components revealed that (1) rivaroxaban decreased the most severe ischemic events and (2) that across different efficacy and safety outcomes, results consistently supported a favorable benefit–risk profile. These results help inform shared decision making on the use of rivaroxaban 2.5 mg twice daily with daily antiplatelet therapy.RegistrationURL: https://www.clinicaltrials.gov; unique identifier: NCT02504216.

To summarize the implementation approaches and updating methods of clinically implemented models and consecutively advise researchers on the implementation and updating. We included studies describing the implementation of prognostic binary prediction models in a clinical setting. We retrieved articles from Embase, Medline, and Web of Science from January 1, 2010, to January 1, 2024. We performed data extraction, based on Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis and Prediction Model Risk of Bias Assessment guidelines, and summarized. The search yielded 1872 articles. Following screening, 37 articles, describing 56 prediction models, were eligible for inclusion. The overall risk of bias was high in 86% of publications. In model development and internal validation, 32% of the models was assessed for calibration. External validation was performed for 27% of the models. Most models were implemented into the hospital information system (63%), followed by a web application (32%) and a patient decision aid tool (5%). Moreover, 13% of models have been updated following implementation. Impact assessments generally showed successful model implementation and the ability to improve patient care, despite not fully adhering to prediction modeling best practice. Both impact assessment and updating could play a key role in identifying and lowering bias in models.