Abstract
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter’s syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring.
Highlights
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods
Quantification of mutant allele fraction (MAF) by either Targeted amplicon deep sequencing (TS) or digital PCR (dPCR) showed excellent correlation (Supplementary Fig. 1). circulating tumour DNA (ctDNA) was detectable in all 25 cases and comprised between 0.1 and 90% of total circulating DNA
The bulky lymphadenopathy was markedly reduced and this compartmentalized disease response was matched by a significant reduction in ctDNA (Fig. 1c). These findings reveal the ability of ctDNA analysis to simultaneously track tumour kinetics across multiple disease sites and suggest that ctDNA may be further useful in cases where disease is predominantly confined to the tissues such as small lymphocytic lymphoma
Summary
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. DNA (ctDNA) is readily detectable in patients with CLL. CtDNA does not mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter’s syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring. Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia. CD20 and CD52 heralded the beginning of the targeted therapy revolution[1] and these antibodies have since been joined by small molecule inhibitors, which target phosphoinositide
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