@article{John R. Jones_Niels Weinhold_Cody Ashby_Brian A. Walker_Chris Wardell_Charlotte Pawlyn_Leo Rasche_Lorenzo Melchor_David A. Cairns_Walter M. Gregory_David Johnson_Dil B. Begum_Sidra Ellis_Amy L. Sherborne_Gordon Cook_Martin F. Kaiser_Mark T. Drayson_Roger G. Owen_Graham H. Jackson_Faith E. Davies_Mel Greaves_Gareth J. Morgan_2019, place={Pavia, Italy}, title={Clonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients}, volume={104}, url={https://haematologica.org/article/view/8974}, DOI={10.3324/haematol.2018.202200}, abstractNote={The emergence of treatment resistant sub-clones is a key feature of relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent relapse include maximizing response and the use of maintenance therapy. We used whole exome sequencing to study the genetics of paired samples taken at presentation and at relapse from 56 newly diagnosed patients, following induction therapy, randomized to receive either lenalidomide maintenance or observation as part of the Myeloma XI trial. Patients included were considered high risk, relapsing within 30 months of maintenance randomization. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterized by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumor suppressor genes, and acquired structural aberrations. Conversely, in patients achieving a partial response, the evolutionary features were predominantly stable with a similar mutational and structural profile seen at both time points. There were no significant differences between patients relapsing after lenalidomide maintenance <em>versus</em> observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse. This trial is registered at <em><a href="http://clinicaltrials.gov">clinicaltrials.gov</a> identifier: 01554852</em&gt;.}, number={7}, journal={Haematologica}, author={John R. Jones and Niels Weinhold and Cody Ashby and Brian A. Walker and Chris Wardell and Charlotte Pawlyn and Leo Rasche and Lorenzo Melchor and David A. Cairns and Walter M. Gregory and David Johnson and Dil B. Begum and Sidra Ellis and Amy L. Sherborne and Gordon Cook and Martin F. Kaiser and Mark T. Drayson and Roger G. Owen and Graham H. Jackson and Faith E. Davies and Mel Greaves and Gareth J. Morgan}, year={2019}, month={Jun.}, pages={1440-1450} }