Clinical applications of genetic sequencing in lymphoma: A retrospective review

• Published in: Journal of clinical oncology Vol. 35; no. 15_suppl; p. e23169
• Main Authors: Shango, Maryann, Devata, Sumana, Wilcox, Ryan A., Phillips, Tycel Jovelle
• Format: Journal Article
• Language: English
• Published: 20.05.2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.15_suppl.e23169

Abstract only 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 3 rd line therapies and everolimus was 5 th . 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.