Pre-treatment circulating tumor DNA as a biomarker for disease burden in diffuse large B cell lymphoma (DLBCL).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8539-8539
Author(s):  
Florian Scherer ◽  
David Matthew Kurtz ◽  
Michael Richard Green ◽  
Aaron M. Newman ◽  
Daniel M. Klass ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Burden ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Large B Cell Lymphoma ◽  
Pre Treatment ◽  
Tumor Dna ◽  
Large B Cell

Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR-T therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7552-7552 ◽  
Author(s):  
Saurabh Dahiya ◽  
Ryan Le ◽  
Nasheed Mohammad Hossain ◽  
Matthew Abramian ◽  
Lori S. Muffly ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Pcr Amplification ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Circulating Tumor Dna ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Tumor Dna ◽  
Large B Cell

7552 Background: Circulating tumor DNA(CTD) have been used for disease monitoring in Diffuse Large B Cell Lymphoma(DLBCL) (Kurtz ASCO 2016). Role of CTD assessment in DLBCL patients treated with CAR-T therapy has not been studied. We prospectively analyzed CTD of dynamics measured by next generation sequencing(NGS) of BCR using ClonoSeq MRD(Adaptive Biotechnologies), before and after CAR-T therapy to determine feasibility and clinical utility. Methods: At Stanford, 7 patients were enrolled on ZUMA-1 clinical trial NCT02348216, treating chemo-refractory DLBCL patients with anti-CD19, CAR-T. Complete radiologic data and CTD analysis was collected for six subjects. Tumor-DNA was extracted from archival paraffin-embeded tissue & analyzed using the NGS-based assay. PCR amplification of IGH-VDJ, IGH-DJ & IGK regions using universal consensus primers was performed followed by NGS to determine the tumor clonotype(s). Blood collected at day 0,7,14,28,60 & 90 days in relation to CAR-T infusion was used to detect CTD by ClonoSeq quantification of clonotypes. Results: Clonotypes were successfully determined for all 6 subjects, and 30 blood samples for 6 patients were prospectively analyzed. All patients had measurable disease burden pre-CAR-T infusion. CTD dynamics correlated with PET-CT outcomes in 100% of the patients. Increasing CTD temporally preceded progressive disease(PD) before PETCT recognition in 4 of 5 patients and was always increasing when PETCT showed PD. Preceding CTD quantification correlated with disease volume increase. One patient achieved durable KTE-19 complete response(CR) and detectable CTD became undetectable on day 14(and on subsequent samples) following CAR-T infusion, corresponding to 1 & 3 month PETCT CR. Additionally, the burden of disease measured by lymphoma molecules per ml allowed volumetric response assessment in all the patients who experienced massive reduction in tumor volume, but by traditional response definition had partial response. Conclusions: ClonoSeq CTD provides precise total tumor quantification of DLBCL in the CAR-T cell setting. This technology may overcome fundamental limitations of DLBCL imaging(cost, radiation exposure & limited repetition).

Circulating tumor DNA: clinical roles in diffuse large B cell lymphoma

2018 ◽  
Vol 98 (2) ◽  
pp. 255-269 ◽  
Author(s):  
Fang-Tian Wu ◽  
Luo Lu ◽  
Wei Xu ◽  
Jian-Yong Li
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Large B Cell Lymphoma ◽  
Tumor Dna ◽  
Large B Cell

MUTATIONAL LANDSCAPE OF DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) AT DIAGNOSIS AND AT PROGRESSION ASSESSED BY CIRCULATING TUMOR DNA ANALYSIS

2019 ◽  
Vol 37 ◽  
pp. 186-187
Author(s):  
A. Rivas-Delgado ◽  
F. Nadeu ◽  
A. Enjuanes ◽  
L. Magnano ◽  
N. Castrejón de Anta ◽  
...  
Keyword(s):  
B Cell ◽  
Dna Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Mutational Landscape ◽  
Large B Cell Lymphoma ◽  
Tumor Dna ◽  
Large B Cell

Elucidation of distinct mutational patterns between diffuse large B cell lymphoma subtypes utilizing circulating tumor DNA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7538-7538 ◽  
Author(s):  
Joanne Soo ◽  
David Matthew Kurtz ◽  
Florian Scherer ◽  
Alexander F.M. Craig ◽  
Michael C. Jin ◽  
...  
Keyword(s):  
B Cell ◽  
Molecular Subtypes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Targeted Sequencing ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Tumor Dna ◽  
Large B Cell

7538 Background: Patients with diffuse large B cell lymphoma (DLBCL) exhibit significant differences in clinical outcome based on cell-of-origin (COO). Patients are categorized as having germinal-center-like (GCB) or activated-B-cell-like (ABC) disease based on RNA microarray and histopathological analyses of tumor biopsies. We recently described an accurate sequencing-based method for determination of COO in DLBCL utilizing stereotyped differences in mutations (Scherer et al., 2016). Here, we further explore the mutational patterns in patients with differing molecular subtypes of DLBCL based on sequencing of circulating tumor DNA. Methods: We applied cancer personalized profiling by deep sequencing (CAPP-Seq) to pretreatment plasma samples and matched germline from a cohort of 115 patients with DLBCL. We then identified somatic alterations, which were used to determine COO molecular subtypes as previously described. Finally, we compared mutational patterns in patients with GCB and non-GCB DLBCL. Results: We detected a significantly greater number of total mutations (GCB: 1766 ± 160 mutations per Mb of targeted sequencing; non-GCB: 1364 ± 150 mutations per Mb of targeted sequencing; p < 0.05) and coding mutations (GCB: 145 ± 21 mutations per Mb of targeted sequencing; non-GCB: 28 ± 8.5 mutations per Mb of targeted sequencing; p < 0.001), particularly in immunoglobulin (Ig) regions (p < 0.05). In addition, GCB and non-GCB samples exhibited distinct mutational patterns within Ig regions. GCB samples were enriched for mutations in regions of switch mu (Sμ) (p < 0.01) and IGHV2-70 (p < 0.01), while non-GCB samples were enriched for mutations in regions of IGHG3 (p < 0.03), IGHV4-34 (p < 0.03), and IGLL5 (p < 0.05). GCB samples were also significantly enriched for coding mutations in SOCS1 (p < 0.01), a gene not included in our original COO classifier. Conclusions: Patients with GCB and non-GCB DLBCL exhibit distinct mutational patterns across both Ig and non-Ig loci of the genome. These differences in mutational patterns can be used to classify molecular subtypes noninvasively, potentially providing further utility to noninvasive genotyping and liquid biopsies.

Monitoring of Circulating Tumor DNA Improves Early Relapse Detection After Axicabtagene Ciloleucel Infusion in Large B-Cell Lymphoma: Results of a Prospective Multi-Institutional Trial

2021 ◽  
pp. JCO.21.00377
Author(s):  
Matthew J. Frank ◽  
Nasheed M. Hossain ◽  
Ali Bukhari ◽  
Erin Dean ◽  
Jay Y. Spiegel ◽  
...  
Keyword(s):  
B Cell ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Circulating Tumor Dna ◽  
Large B Cell Lymphoma ◽  
Tumor Dna ◽  
Large B Cell

PURPOSE Although the majority of patients with relapsed or refractory large B-cell lymphoma respond to axicabtagene ciloleucel (axi-cel), only a minority of patients have durable remissions. This prospective multicenter study explored the prognostic value of circulating tumor DNA (ctDNA) before and after standard-of-care axi-cel for predicting patient outcomes. METHODS Lymphoma-specific variable, diversity, and joining gene segments (VDJ) clonotype ctDNA sequences were frequently monitored via next-generation sequencing from the time of starting lymphodepleting chemotherapy until progression or 1 year after axi-cel infusion. We assessed the prognostic value of ctDNA to predict outcomes and axi-cel–related toxicity. RESULTS A tumor clonotype was successfully detected in 69 of 72 (96%) enrolled patients. Higher pretreatment ctDNA concentrations were associated with progression after axi-cel infusion and developing cytokine release syndrome and/or immune effector cell–associated neurotoxicity syndrome. Twenty-three of 33 (70%) durably responding patients versus 4 of 31 (13%) progressing patients demonstrated nondetectable ctDNA 1 week after axi-cel infusion ( P < .0001). At day 28, patients with detectable ctDNA compared with those with undetectable ctDNA had a median progression-free survival and OS of 3 months versus not reached ( P < .0001) and 19 months versus not reached ( P = .0080), respectively. In patients with a radiographic partial response or stable disease on day 28, 1 of 10 patients with concurrently undetectable ctDNA relapsed; by contrast, 15 of 17 patients with concurrently detectable ctDNA relapsed ( P = .0001). ctDNA was detected at or before radiographic relapse in 29 of 30 (94%) patients. All durably responding patients had undetectable ctDNA at or before 3 months after axi-cel infusion. CONCLUSION Noninvasive ctDNA assessments can risk stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.

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