Clinical applications of genetic sequencing in lymphoma: A retrospective review.

e23169 Background: Personalized therapy through the identification of targetable mutations within individual tumors has increasingly become a focus in the management of patients (pts) with relapsed/refractory malignancy. To better understand how this is clinically applied, we reviewed 29 cases of B- and T-cell lymphomas that had genetic sequencing of their tumor. Methods: The electronic medical records of 29 pts who underwent Michigan Oncology Sequencing (MI-ONCOSEQ) testing at the University of Michigan from 2013-2016 were reviewed for disease and treatment history. Reports from whole-genome tumor sequencing were obtained for each patient to identify putative molecular targets. Results: Sixteen male and 13 female pts had a median age of 59 years (range 30-80 years) and median disease stage of IV at diagnosis. Five had CTCL, 5 PTCL, 11 follicular, 1 CLL/ mantle cell (MC), 1 MC, 1 marginal zone, 1 Waldenstrom’s (WM) and 4 DLBCL. Pts received a median of 2 therapies prior to MI-ONCOSEQ biopsy. Targetable mutations were identified in 15 pts and a total of 5 pts underwent MI-ONCOSEQ-based treatments. Bosutinib was given for FYB-FGR fusion, imatinib for FLI1-PDGFRB fusion, and everolimus for activating mTOR mutation with an avg. treatment duration of 3.6 weeks due to progressive disease. Bosutinib and imatinib were 3rd line therapies and everolimus was 5th. Another 2 pts were treated with ibrutinib for transformed WM with MYD88 mutation and bortezomib after classification of DLBCL as ABC-type based on MI-ONCOSEQ results, with CR in both. Other targetable mutations identified include BRAF, CDK, BCL2, EZH2 and NOTCH. Of the remaining 12 pts with targetable mutations, 8 pursued clinical trials, 2 responded to standard therapy, 1 died shortly after genetic analysis and 1 declined further therapy. About 50% of these pts remain alive. Conclusions: Our results demonstrate that targeted therapy is favored after standard therapy or clinical trial options are exhausted. Barriers to its use include the availability of clinical trials, off-label drug access and our incomplete knowledge of driver mutations. With further understanding of disease pathogenesis, we expect personalized therapy will be possible for all patients.