Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear. Materials and Methods We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes. Results Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression. Conclusion Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.
Abstract
Purpose The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear. Materials and Methods We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes. Results Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression. Conclusion Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.
참고문헌 (38)
- Swerdlow SH, "The 2016 revision of the World Health Organization classification of lymphoid neoplasms", Blood, 127, pp.2375~2390 (2016)
- Teras LR, "2016 US lymphoid malignancy statistics by World Health Organization subtypes", CA Cancer J Clin, 66, pp.443~459 (2016)
- Dreyling M, "Newly diagnosed and relapsed follicular lymphoma : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up", Ann Oncol, 27, pp.v83~v90 (2016)
- Hiddemann W, "Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone(CHOP)significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone : results of a prospective randomized study of the German Low-Grade Lym-phoma Study Group", Blood, 106, pp.3725~3732 (2005)
- Marcus R, "Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma", J Clin Oncol, 26, pp.4579~4586 (2008)
- Rummel MJ, "Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for pati-ents with indolent and mantle-cell lymphomas : an open-label, multicentre, randomised, phase 3 non-inferiority trial", Lancet, 381, pp.1203~1210 (2013)
- Schulz H, "Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma : a systematic review and meta-analysis", J Natl Cancer Inst, 99, pp.706~714 (2007)
- Marcus R, "Obinutuzumab for the first-line treatment of follicular lymphoma", N Engl J Med, 377, pp.1331~1344 (2017)
- Flinn IW, "Randomized trial of bendamustine-rituximab or R-CHOP", R-CVP in first-line treatment of indolent NHL or MCL : the BRIGHT study, 2014, pp.123, 2944~2952
- Bachy E, "Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma : long-term results of the PRIMA study", J Clin Oncol, 37, pp.2815~2824 (2019)
- Casulo C, "Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death : an analysis from the National LymphoCare Study", J Clin Oncol, 33, pp.2516~2522 (2015)
- Seymour JF, "Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma : benefit of obinutuzumab in reducing the rate of early progression", Haematologica, 104, pp.1202~1208 (2019)
- Wagner-Johnston ND, "Outcomes of transformed follicular lymphoma in the modern era : a report from the National LymphoCare Study(NLCS)", Blood, 126, pp.851~857 (2015)
- Freeman CL, "Early progression after bendamustine-rituximab is associated with high risk of transformation in advanced stage follicular lymphoma", Blood, 134, pp.761~764 (2019)
- Yoon SE, "Impact of transformation on the survival of patients diagnosed with follicular lymphoma that progressed within 24 months", J Cancer, 12, pp.2488~2497 (2021)
- Diaz LA Jr, "Liquid biopsies : genotyping circulating tumor DNA", J Clin Oncol, 32, pp.579~586 (2014)
- Camus V, "Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring : a prospective study", Haematologica, 106, pp.154~162 (2021)
- Lakhotia R, "Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma", Blood Adv, 6, pp.2667~2680 (2022)
- Herrera AF, "Risk profiling of patients with relapsed", refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA, 2022, pp.6, 1651~1660
- Freedman A, "Follicular lymphoma : 2020 update on diagnosis and management", Am J Hematol, 95, pp.316~327 (2020)
- Solal-Celigny P, "Follicular lymphoma international prognostic index", Blood, 104, pp.1258~1265 (2004)
- Cheson BD, "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma : the Lugano classification", J Clin Oncol, 32, pp.3059~3068 (2014)
- Tobin JW, "Progression of disease within 24 months in follicular lymphoma is associated with reduced intratumoral immune infiltration", J Clin Oncol, 37, pp.3300~3309 (2019)
- Pastore A, "Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma : a retrospective analysis of a prospective clinical trial and validation in a population-based registry", Lancet Oncol, 16, pp.1111~1122 (2015)
- Carbone A, "Follicular lymphoma", Nat Rev Dis Primers, 5, pp.83~ (2019)
- Green MR, "Chromatin modifying gene mutations in follicular lymphoma", Blood, 131, pp.595~604 (2018)
- O’Shea D, "The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival", Blood, 112, pp.3126~3129 (2008)
- McKenna A, "The Genome Analysis Toolkit : a MapReduce framework for analyzing next-generation DNA sequencing data", Genome Res, 20, pp.1297~1303 (2010)
- Li H, "A statistical framework for SNP calling, mutation discovery, association mapping and population genetical para-meter estimation from sequencing data", Bioinformatics, 27, pp.2987~2993 (2011)
- Newman AM, "Integrated digital error suppression for improved detection of circulating tumor DNA", Nat Biotechnol, 34, pp.547~555 (2016)
- McLaren W, "The Ensembl variant effect predictor", Genome Biol, 17, pp.122~ (2016)
- Avanzini S, "A mathematical model of ctDNA shedding predicts tumor detection size", Sci Adv, 6, pp.eabc4308~ (2020)
- Cho J, "Comparison of tumor mutation burden of 300 various non-Hodgkin lymphomas using panel based massively parallel sequencing", BMC Cancer, 21, pp.972~ (2021)
- Shin SH, "Analysis of circulating tumor DNA by targeted ultra-deep sequencing across various non-Hodgkin lymphoma subtypes", Leuk Lymphoma, 60, pp.2237~2246 (2019)
- Yoon SE, "Plasma circulating tumor DNA in patients with primary central nervous system lymphoma", Cancer Res Treat, 54, pp.597~612 (2022)
- Hur JY, "Plasma cell-free DNA is a prognostic biomarker for survival in patients with aggressive non-Hodgkin lymphomas", Ann Hematol, 99, pp.1293~1302 (2020)
- Kim SJ, "Circulating tumor DNA-based genotyping and monitoring for predicting disease relapses of patients with peripheral T-cell lymphomas", Cancer Res Treat, 55, pp.291~303 (2023)
- Kim JJ, "In-depth circulating tumor DNA sequencing for prognostication and monitoring in natural killer", T-cell lymphomas, 2023, pp.13, 1109715~