Multimodal explorative testing in the ON-OFF ibrutinib trial in CLL
November 28, 2025 @ 09:00 – 09:30 CET
Multimodal explorative testing in the ON-OFF ibrutinib trial in CLL
Richard Rosenquist Brandell, Karolinska Institutet & Karolinska University Hospital
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the Western World and displays substantial variability in clinical course, ranging from indolent disease requiring no therapy to highly aggressive forms with short survival despite treatment. Although the past decade has seen major advances in drug development, CLL remains incurable. Targeted therapies, particularly Bruton’s tyrosine kinase inhibitors (BTKi), have become central to CLL management. However, continuous long-term BTKi administration, such as with ibrutinib, is associated with considerable significant side-effects, including cardiac arrhythmias. Furthermore, despite its proven efficacy in both treatment-naïve and relapsed/refractory CLL, resistance to ibrutinib continues to challenge durable disease control. To address these limitations, we conducted a phase 1b/2 prospective, single-arm, multicenter study evaluating controlled treatment cessation as a strategy to preserve tolerability and maintain sensitivity to ibrutinib, while also improving cost-effectiveness. The study protocol incorporated serial blood sampling prior to treatment initiation and throughout on/off treatment periods. Here, we leverage this unique longitudinal sample collection to perform multimodal profiling, including genomic and transcriptomic sequencing as well as proteomics, to investigate mechanisms of drug response and resistance. We provide an update on the current status of the study and ongoing analyses.
Biography
Richard Rosenquist Brandell is Professor of Clinical Genetics at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and Senior Physician in Clinical Genetics at Karolinska University Hospital, Sweden. Focusing on hematological malignancies and utilizing high-throughput sequencing and other innovative technologies, his research team has identified novel prognostic and predictive biomarkers that have refined disease classification and significantly improved patient risk-stratification and clinical decision-making. Richard Rosenquist Brandell initiated and led the Clinical Genomics Unit within Science for Life Laboratory (SciLifeLab) in Uppsala (2013-2017) and was platform director for the Clinical Genomics platform (2016-2021) within SciLifeLab, which includes seven Clinical Genomics units across Sweden. He is currently Director of Genomic Medicine Sweden (GMS), a national infrastructure for implementation of precision medicine. Rosenquist Brandell is a member of the Nobel Assembly at Karolinska Institutet.
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