Next-Generation Sequencing-Based Monitoring of Circulating Tumor DNA Reveals Clonotypic Heterogeneity in Untreated PTCL

Miljković, Miloš D.; Melani, Christopher; Pittaluga, Stefania; Lakhotia, Rahul; Lucas, Nicole; Jacob, Allison P.; Yusko, Erik; Jaffe, Elaine S.; Wilson, Wyndham H.; Roschewski, Mark

doi:10.1182/bloodadvances.2020003679

Cited by 11 publications

(11 citation statements)

References 42 publications

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“…However, in a previous study with 20 patients, it was not possible to demonstrate an association between mutations and clinical parameters or survival [132]. Milkjovic et al used dPCR to detect TCR rearrangements in 34 patients with peripheral T cell lymphoma (PTCL), and reported that a median 2.6-log decrease in their ctDNA level after the first two cycles of treatment and that early clearance of ctDNA after cycle 2 was not associated with a statistically significant improvement in EFS (median (95% CI), 8.4 (0.1-NR) vs. 2.0 (0.1-NR) years; p = 0.32) or OS (median, 8.4 (0.3-NR) vs. 7.0 (0.5-NR) years; p = 0.44) [133].…”

Section: T Cell Lymphomasmentioning

confidence: 90%

“…Additionally, Spina et al reported that a greater than 2-log reduction in cfDNA between diagnosis and after two chemotherapy courses was linked to a complete metabolic response and cure, but these studies have several limitations and more evidence is needed to incorporate liquid biopsies into the monitoring of MRD in lymphomas [133,137].…”

Section: Hodgkin Lymphomamentioning

confidence: 99%

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Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

Colmenares¹,

Álvarez²,

Barrio³

et al. 2022

Preprint

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The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsy. Most of the studies about this topic have been focused on B cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for diagnosis and minimal residual monitoring in B cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real-time. However, there are limitations such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess minimal residual disease or the lack of standardization of the method and clinical studies to confirm its prognostic impact. This review focuses on clinical applications of cfDNA on minimal residual disease in hematological malignancies.

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Section: T Cell Lymphomasmentioning

confidence: 90%

Section: Hodgkin Lymphomamentioning

confidence: 99%

Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

Colmenares¹,

Álvarez²,

Barrio³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…However, in a previous study with 20 patients, it was not possible to demonstrate an association between mutations and the clinical parameters or survival [ 129 ]. Milkjovic et al used dPCR to detect TCR rearrangements in 34 patients with peripheral T-cell lymphomas (PTCL), and reported a median 2.6-log decrease in their ctDNA levels after the first two cycles of treatment, as well as the early clearance of ctDNA after cycle 2, were not associated with a statistically significant improvement in EFS (median (95% CI), 8.4 (0.1–NR) vs. 2.0 (0.1–NR) years; p = 0.32) or OS (median, 8.4 (0.3–NR) vs. 7.0 (0.5–NR) years; p = 0.44) [ 130 ].…”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

“…Additionally, Spina et al reported that a two-log reduction in cfDNA, or greater, between the diagnosis and after the two chemotherapy courses, was linked to a complete metabolic response and cure. However, these studies have several limitations, and more evidence is needed to incorporate liquid biopsies into the monitoring of the MRD in lymphomas [ 130 , 134 ].…”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

Colmenares

Álvarez

Barrio

et al. 2022

Cancers

View full text Add to dashboard Cite

The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising, and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing a greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsies. Most of the studies about this topic have focused on B-cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for the diagnosis and minimal residual monitoring of B-cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of the early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real time. However, there are limitations, such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess the minimal residual disease, or the lack of standardization of the method, and clinical studies, to confirm its prognostic impact. This review focuses on the clinical applications of cfDNA on the minimal residual disease in hematological malignancies.

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“…High levels of ctDNA pre-treatment correlate with advanced disease stage, and worse prognosis in many subtypes of lymphoma, including DLBCL [ 114 - 116 ] , FL [ 117 - 119 ] , and MCL [ 120 ] . Real-time monitoring of ctDNA level during therapy has been explored in a variety of lymphoma subtypes including DLBCL [ 114 ] , FL [ 119 ] , HL [ 121 ] , MCL [ 122 , 123 ] , and PTCL [ 124 ] , and preliminary studies demonstrate that changes in ctDNA can predict clinical outcomes including end of treatment response and risk of progression after completion of treatment. For example, a recent study demonstrated that monitoring of ctDNA improves early relapse detection after Axicabtagene Ciloleucel CAR T-cell therapy in DLBCL [ 125 ] .…”

Section: Prediction Of Response To Therapymentioning

confidence: 99%

Barriers to achieving a cure in lymphoma

Kambhampati¹,

Song²,

Herrera³

et al. 2021

CDR

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Lymphoma is a diverse disease with a variety of different subtypes, each characterized by unique pathophysiology, tumor microenvironment, and underlying signaling pathways leading to oncogenesis. With our increasing understanding of the molecular biology of lymphoma, there have been a number of novel targeted therapies and immunotherapy approaches that have been developed for the treatment of this complex disease. Despite rapid progress in the field, however, many patients still relapse largely due to the development of drug resistance to these therapies. A better understanding of the mechanisms underlying resistance is needed to develop more novel treatment strategies that circumvent these mechanisms and design better treatment algorithms that personalize therapies to patients and sequence these therapies in the most optimal manner. This review focuses on the recent advances in therapies in lymphoma, including targeted therapies, monoclonal antibodies, antibody-drug conjugates, cellular therapy, bispecific antibodies, and checkpoint inhibitors. We discuss the genetic and cellular principles of drug resistance that span across all the therapies, as well as some of the unique mechanisms of resistance that are specific to these individual classes of therapies and the strategies that have been developed to address these modes of resistance.

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Next-Generation Sequencing-Based Monitoring of Circulating Tumor DNA Reveals Clonotypic Heterogeneity in Untreated PTCL

Cited by 11 publications

References 42 publications

Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

Barriers to achieving a cure in lymphoma

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