دورية أكاديمية
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.
| العنوان: | 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. |
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| المؤلفون: | Frank MJ; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA., Hossain NM; Loyola University Chicago, Stritch School of Medicine, Maywood, IL., Bukhari A; University of Maryland School of Medicine, Greenebaum Comprehensive Cancer Center, Baltimore, MD., Dean E; Moffitt Cancer Center, Tampa, FL., Spiegel JY; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA., Claire GK; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA., Kirsch I; Adaptive Biotechnologies, Seattle, WA., Jacob AP; Adaptive Biotechnologies, Seattle, WA., Mullins CD; Adaptive Biotechnologies, Seattle, WA., Lee LW; Adaptive Biotechnologies, Seattle, WA., Kong KA; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA., Craig J; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA., Mackall CL; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA.; Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, CA., Rapoport AP; University of Maryland School of Medicine, Greenebaum Comprehensive Cancer Center, Baltimore, MD., Jain MD; Moffitt Cancer Center, Tampa, FL., Dahiya S; University of Maryland School of Medicine, Greenebaum Comprehensive Cancer Center, Baltimore, MD., Locke FL; Moffitt Cancer Center, Tampa, FL., Miklos DB; Division of Blood and Stem Cell Transplantation, Department of Medicine, Stanford University, Stanford, CA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2021 Sep 20; Vol. 39 (27), pp. 3034-3043. Date of Electronic Publication: 2021 Jun 16. |
| نوع المنشور: | Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Biological Products/*therapeutic use , Circulating Tumor DNA/*genetics , Lymphoma, Large B-Cell, Diffuse/*drug therapy, Adult ; Aged ; Biological Products/pharmacology ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Prospective Studies ; Young Adult |
| مستخلص: | 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. Competing Interests: Matthew J. FrankEmployment: Roche/GenentechStock and Other Ownership Interests: Roche/Genentech Ilan KirschEmployment: Adaptive BiotechnologiesStock and Other Ownership Interests: Adaptive Biotechnologies Allison P. JacobEmployment: Adaptive BiotechnologiesStock and Other Ownership Interests: Adaptive Biotechnologies Chelsea D. MullinsEmployment: Adaptive BiotechnologiesStock and Other Ownership Interests: Adaptive Biotechnologies Lik Wee LeeEmployment: Adaptive Biotechnologies Crystal L. MackallStock and Other Ownership Interests: Lyell Immunopharma, Alimera Sciences, Vor Pharmaceuticals, Apricity Health, Syncopation Life SciencesConsulting or Advisory Role: Bryology, Vor Biopharma, Apricity Health, TPG, Alimera Sciences, PACT Pharma, Nektar, Lyell Immunopharma, NeoImmuneTech, Syncopation Life Sciences, NeoImmuneTech, Bristol Myers Squibb, ImmaticsResearch Funding: Lyell ImmunopharmaPatents, Royalties, Other Intellectual Property: I am an inventor on numerous patents related to chimeric antigen receptor therapeutics and received royalties from NIH for the CD22-CAR patent licensed to Juno therapeuticsTravel, Accommodations, Expenses: NeoImmuneTech, Roche, NektarOther Relationship: Lyell Immunopharma Michael D. JainConsulting or Advisory Role: Kite/Gilead, Novartis, Bristol Myers Squibb, TakedaTravel, Accommodations, Expenses: Kite/Gilead Saurabh DahiyaConsulting or Advisory Role: Kite/Gilead, Atara Biotherapeutics Frederick L. LockeConsulting or Advisory Role: Novartis, Celgene, GammaDelta Therapeutics, Calibr, WUGEN Inc, Alimera Sciences, Cellular Biomedicine Group, Gerson Lehrman Group, EcoR1 Capital, Amgen, Bluebird Bio, Bristol Myers Squibb, Iovance Biotherapeutics, Legend Biotech, CowenResearch Funding: Kite, a Gilead company, Alimera Sciences, NovartisPatents, Royalties, Other Intellectual Property: Double Mutant Survivin Vaccine. US010414810B2, CAR T Cells with Enhanced Metabolic Fitness. Serial Number: 62/939727, Methods of Enhancing CAR T Cell Therapies. Serial Number: 62/892292, Evolutionary Dynamics of Non-Hodgkin Lymphoma CAR-T cell therapy. Serial Number: 62/879534Travel, Accommodations, Expenses: Kite, a Gilead company David B. MiklosConsulting or Advisory Role: Kite, a Gilead company, Adaptive Biotechnologies, Novartis, Juno/Celgene, Pharmacyclics, Janssen, Precision Biosciences, Alimera Sciences, Miltenyi BiotecResearch Funding: Pharmacyclics, Novartis, Roche/Genentech, Kite, a Gilead company, Adaptive Biotechnologies, Alimera Sciences, Precision BiosciencesPatents, Royalties, Other Intellectual Property: Patent held with Pharmacyclics supporting Ibrutinib for cGVHD (no royalty claim).Travel, Accommodations, Expenses: Kite, a Gilead company, Pharmacyclics/Janssen, Adaptive Biotechnologies, Juno Therapeutics, Miltenyi Biotec, NovartisNo other potential conflicts of interest were reported. |
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| معلومات مُعتمدة: | P30 CA076292 United States CA NCI NIH HHS; T32 HL007952 United States HL NHLBI NIH HHS; K08 CA248968 United States CA NCI NIH HHS; P01 CA049605 United States CA NCI NIH HHS; P30 CA124435 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Biological Products) 0 (Circulating Tumor DNA) U2I8T43Y7R (axicabtagene ciloleucel) |
| تواريخ الأحداث: | Date Created: 20210616 Date Completed: 20211124 Latest Revision: 20230510 |
| رمز التحديث: | 20230512 |
| مُعرف محوري في PubMed: | PMC10166351 |
| DOI: | 10.1200/JCO.21.00377 |
| PMID: | 34133196 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.21.00377 |