Due to the rapidly evolving landscape of targeted therapies, there is an unmet need for comprehensive molecular profiling to guide treatment decisions for patients with large B-cell lymphoma (LBCL). Therefore, we designed a pilot study to assess the feasibility and turnaround time (TAT) of a comprehensive whole exome sequencing (WES) and transcriptome sequencing (RNA-seq) assay in patients with LBCL (NCT05464823). Patients aged ≥18 years with LBCL were eligible. Formalin-fixed paraffin-embedded tissues at diagnosis or recurrence underwent WES, RNA-seq, and copy number analysis with concomitant germline DNA sequencing. Genomic and transcriptomic data were profiled to define various LBCL signatures such as cell-of-origin (COO), dark zone signature (DZsig), LymphGen and lymphoma microenvironment (LME) classification. Among 100 patients enrolled, samples from 71 patients (48 with newly diagnosed and 23 with relapsed/refractory disease) passed pathology quality control and underwent WES and RNA-seq analysis and reporting. The median TAT was 8 days for individual patient reports (range: 6-22 days), with 73% of reports delivered ≤10 days. Applying molecular risk classification, high risk event-free survival within 24 months (EFS24) signature was associated with DZsig and LME, but not with COO or LymphGen indicating the complex heterogeneity of the disease. We demonstrated the clinical utility and acceptable TAT of a comprehensive WES and RNA-seq assay for LBCL managed in routine clinical practice. These findings support the real-world feasibility of using integrated WES and RNA-seq to define molecular subgroups, guide clinical decision-making at the time of a new line of therapy, and enable biology based subtype-driven clinical trials.
Dai Chihara, Kumudha Balakrishnan, G. Masand et al.· Blood Advances· 0 citations
Lymphomas comprise a complex and heterogeneous group of malignancies which pose challenges in understanding their epidemiology, pathobiology, treatment responses and long-term outcomes. Evolving diagnostic classification and fast-paced therapy development compound these challenges. Robust real-world data (RWD) collection and analysis using clinical registries can contribute significantly to address gaps in understanding of practice variation and provide evidence for health technology assessments. However, to maximize the impact of lymphoma registries, and those in other diseases, there is a compelling need for global collaboration, data harmonization and automated integration between registries and other large datasets. Technologies that enable safer data sharing are already available, but historical legal frameworks and evolving privacy concerns are not keeping pace, undermining their intended purpose and limiting the full potential of available high-quality RWD to improve patient care. This White Paper written by the Global Lymphoma Registry Alliance (LyRA) discusses the importance and value of lymphoma registries for different stakeholders as well as benefits of forming a global alliance of the registry network. An alliance such as LyRA serves both academic endeavors and public interest through collaboration between patient and community organizations, policy-makers, regulatory authorities, industry and others seeking to use RWD. Bringing these stakeholders together and raising awareness more broadly will facilitate timely clinical trial result contextualization and innovation in public-private collaborations on novel trial emulations and designs, including external comparator cohorts. The LyRA leadership propose strategies for overcoming barriers to facilitate these key collaborations towards improving patient outcomes on a global scale.
Eliza A. Hawkes, E. Chung, M. Bishton et al.· Haematologica· 0 citations
