Proceedings of the Annual Meeting of the Austrian Society of Haematology and Medical Oncology

Proceedings of the Annual Meeting of the Austrian Society of Haematology and Medical Oncology 3 1 3 A01 Clonal evolution in relapsed or refractory Diffuse large B cell lymphoma Thomas Melchardt1, Clemens Hufnagl1, Lukas Weiss1, Nadja Kopp2, David Weinstock2, Daniel Neureiter3, Wolfgang Tränkenschuh3, Richard Greil1, Oliver Weigert4, Alexander Egle1 1 Department of Internal Medicine III, Paracelsus Private Medical University, Salzburg, Austria 2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA 3 Institute of Pathology, Paracelsus Private Medical University, Salzburg, Austria 4 Department of Internal Medicine III, Ludwig-Maximilians University, Munich, Germany Introduction: Multiple mutations associated with the biology of diffuse large b-cell lymphoma (DLBCL) have been identified, but there is only little information available about the role of certain mutations and their mechanisms in clonal evolution during relapse. Material and Methods: We identified 27 patients with available histologically confirmed relapsed or refractory DLBCL in a cohort of 346 consecutively treated patients. Primary formalin fixed paraffin embedded tumor sample, sample of refractory or relapsed disease and matched germ line were available for targeted next generation sequencing. A targeted exon capture and next-generation sequencing of all coding exons of 104 selected genes known to be frequently mutated in lymphoma were performed on a HiSeq 2500. Results: Non-synonymous mutations were present in 74 of the 104 genes tested. Individual tumor samples showed between 0 and 29 non-synonymous mutations (median: 10). Less than six non-synonymous mutations in the primary tumor were associated with a better median OS than more mutations (28 versus 15 months p = 0.031). The “early divergent” and the “late divergent” patterns of evolution, previously described in a limited set of patients using VDJ rearrangements, were validated in our cohort using NGS data and showed no influence on the clinical outcome. We also observed that different genes win in clonal selection during treatment challenge compared to lymphoma development. Conclusions: Targeted re-sequencing is a feasible and informative approach in FFPE-fixed DLBCL. Three major types of clonal evolution; large global change, subclonal selection and no or minimal change assuming preprogrammed resistance; were detected during relapse.