<p>Disease progression has been increasingly appreciated with the use of ibrutinib to treat chronic lymphocytic leukemia (CLL). Understanding the pattern of clonal evolution and transcriptomic changes during the early treatment period with ibrutinib may provide insight into the mechanisms of resistance. We performed whole exome sequencing on sequential samples with matched germline controls from 61 patients with CLL during the first 12 months of ibrutinib monotherapy or ibrutinib in combination with rituximab. Additionally, RNA sequencing was done on a subset of 14 patients treated with ibrutinib monotherapy. The presence of clonal shifts was associated with an increased risk of disease progression, suggesting that resistant clones are more likely to emerge in CLL with greater evolutionary capacity.</p><p>This cohort was later augmented with additional data (including data from 15 additional patients). In total, this second set of data contained whole exome sequencing (31 samples),  RNA sequencing (6 samples) and reduced representation bisulfite sequencing (67 samples) for CLL samples and used them to identify expression subtypes of CLL. In an integrative analysis of genetic, transcriptomic, and epigenetic data, incorporating known and newly identified subtypes of CLL, we built new models to improve patient prognostication.</p>

Clonal Evolution and Transcriptomic Analysis of Chronic Lymphocytic    Leukemia Treated with Ibrutinib

14 variables across Demographics, Race and Ethnicity

Clonal Evolution and Transcriptomic Analysis of Chronic Lymphocytic Leukemia Treated with Ibrutinib

Demographics (2)

Race and Ethnicity (1)

Other (11)