Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice.

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with multiple myeloma exposed to three classes of treatment in the single-arm CARTITUDE-1 study. To assess the effectiveness of cilta-cel compared to real-world clinical practice (RWCP), we performed adjusted comparisons using individual patients' data from CARTITUDE-1 and LocoMMotion, a prospective, multinational study of patients with multiple myeloma triple-class exposed of treatment. Comparisons were performed using inverse probability weighting. In CARTITUDE-1, 113 patients were enrolled, and 97 patients were infused with cilta-cel. In LocoMMotion, 248 patients were enrolled, and 170 patients were included in the comparisons versus infused patients. Ninety-two unique regimens were used in LocoMMotion, most frequently carfilzomib-dexamethasone (13.7%), pomalidomide-cyclophosphamide-dexamethasone (13.3%) and pomalidomidedexamethasone (11.3%). Adjusted comparisons showed that patients treated with cilta-cel were 3.12-fold more likely to respond to treatment than those managed by RWCP (response rate, 3.12, 95% confidence interval [95% CI]: 2.24-4.00), had their risk of progression or death reduced to by 85% (progression-free survival hazard ratio=0.15, 95% CI: 0.08-0.29), and a risk of death lowered by 80% (overall survival hazard ratio HR=0.20, 95% CI: 0.09-0.41). The incremental improvement in healthrelated quality of life from baseline for cilta-cel versus RWCP at week 52, as measured by EORTC QLQ-C30 Global Health Status, was 13.4 (95% CI: 3.5-23.6) and increased to 30.8 (95% CI: 21.8-39.8) when including death as additional information regarding patients' health status. Patients treated with cilta-cel experienced more adverse events than those managed with RWCP (any grade: 100% vs. 83.5%). The results from this study demonstrate improved efficacy outcomes of cilta-cel versus RWCP and highlight its potential as a novel and effective treatment option for patients with multiple myeloma triple-class exposed of antimyeloma treatment. CARTITUDE-1 is registered with clinicaltrials gov. Identifier: NCT03548207. LocoMMotion is registered with clinicaltrials gov. Identifier: NCT04035226.

Haematology Outcomes Network in Europe (HONEUR)-A collaborative, interdisciplinary platform to harness the potential of real-world data in hematology.

INTRODUCTION: There remains a need to optimize treatments and improve outcomes among patients with hematologic malignancies. The timely synthesis and analysis of real-world data could play a key role. OBJECTIVES: The Haematology Outcomes Network in Europe (HONEUR) is a federated data network (FDN) that aims to overcome the challenges of heterogenous data collected from different registries, hospitals, and other databases in different countries. It has the functionality required to analyze data from various sources in a time efficient manner, while preserving local data security and governance. With this, research studies can be performed that can increase knowledge and understanding of the management of patients with hematologic malignancies. METHODS: HONEUR uses the Observational Medical Outcomes Partnership (OMOP) common data model, which allows analysis scripts to be run by multiple sites using their own data, ultimately generating aggregated results. Furthermore, distributed analytics can be used to run statistical analyses across multiple sites, as if data were pooled. The external governance model ensures high-quality standards, while data ownership is retained locally. Twenty partners from nine countries are now participating, with data from more than 26 000 patients available for analysis. Research questions that can be addressed through HONEUR include assessments of natural disease history, treatment patterns, and clinical effectiveness. CONCLUSIONS: The HONEUR FDN marks an important step forward in increasing the value of information routinely captured by individual hospitals, registries and other database holders, thus enabling larger-scale studies to be undertaken rapidly and efficiently.

The Value of Federated Data Networks in Oncology: What Research Questions Do They Answer? Outcomes From a Systematic Literature Review.

OBJECTIVES: Real-world evidence (RWE) plays an important role in addressing key research questions of interest to healthcare decision makers. Federated data networks (FDNs) apply novel technology to enable the conduct of RWE studies with multiple partners, without the need to share the individual partner's data set. A systematic review of the published literature was performed to determine which types of research questions can best be addressed through FDNs, specifically in the field of oncology. METHODS: Systematic searches of MEDLINE and Embase were undertaken to identify the types of research questions that had been addressed in studies using FDNs. Additional information was retrieved about study characteristics, statistical methods, and the FDN itself. RESULTS: In total, 40 publications were included where research questions on the following had been addressed (multiple categories possible): disease natural history (58%), safety surveillance (18%), treatment pathways (15%), comparative effectiveness (10%), and cost/resource use studies (3%)-13% of studies had to be left uncategorized. A total of 50% of the studies were run with data partners in networks of ≤5. The size of the networks ranged from 227 patients to >5 million patients. Statistical methods used included distributed learning and distributed regression methods. CONCLUSIONS: Further work is needed to raise awareness of the important role that FDNs can play in leveraging readily available RWE to address key research questions of interest in cancer and the benefits to the research community in engaging in federated data initiatives with a long-term perspective.