The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials
Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1130617/full |
| _version_ | 1797900436413349888 |
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| author | A. Fisher A. Fisher H. Goradia N. Martinez-Calle PEM. Patten PEM. Patten T. Munir |
| author_facet | A. Fisher A. Fisher H. Goradia N. Martinez-Calle PEM. Patten PEM. Patten T. Munir |
| author_sort | A. Fisher |
| collection | DOAJ |
| description | Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly used in routine practice as a prognostic tool, a therapeutic goal, and potentially a trigger for early intervention. Modern therapy for CLL delivers prolonged remissions, causing readout of traditional trial outcomes such as progression-free and overall survival to be inherently delayed. This represents a barrier for the rapid incorporation of novel drugs to the overall therapeutic armamentarium. MRD offers a dynamic and robust platform for the assessment of treatment efficacy in CLL, complementing traditional outcome measures and accelerating access to novel drugs. Here, we provide a comprehensive review of recent major clinical trials of CLL therapy, focusing on small-molecule inhibitors and monoclonal antibody combinations that have recently emerged as the standard frontline and relapse treatment options. We explore the assessment and reporting of MRD (including novel techniques) and the challenges of standardization and provide a comprehensive review of the relevance and adequacy of MRD as a clinical trial endpoint. We further discuss the impact that MRD data have on clinical decision-making and how it can influence a patient’s experience. Finally, we evaluate how upcoming trial design and clinical practice are evolving in the face of MRD-driven outcomes. |
| first_indexed | 2024-04-10T08:46:00Z |
| format | Article |
| id | doaj.art-92cb3c12b1454cdfac4d271d84be91ed |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T08:46:00Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-92cb3c12b1454cdfac4d271d84be91ed2023-02-22T08:50:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.11306171130617The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trialsA. Fisher0A. Fisher1H. Goradia2N. Martinez-Calle3PEM. Patten4PEM. Patten5T. Munir6Division of Cancer Studies and Pathology, University of Leeds, Leeds, United KingdomDepartment of Haematology, Leeds Teaching Hospitals National Health Service (NHS) Trust, Leeds, United KingdomDepartment of Haematology, Nottingham University Hospitals National Health Service (NHS) Trust, Nottingham, United KingdomDepartment of Haematology, Nottingham University Hospitals National Health Service (NHS) Trust, Nottingham, United KingdomDepartment of Haematology, Kings College Hospital National Health Service (NHS) Foundation Trust, London, United KingdomComprehensive Cancer Centre, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomDepartment of Haematology, Leeds Teaching Hospitals National Health Service (NHS) Trust, Leeds, United KingdomMeasurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly used in routine practice as a prognostic tool, a therapeutic goal, and potentially a trigger for early intervention. Modern therapy for CLL delivers prolonged remissions, causing readout of traditional trial outcomes such as progression-free and overall survival to be inherently delayed. This represents a barrier for the rapid incorporation of novel drugs to the overall therapeutic armamentarium. MRD offers a dynamic and robust platform for the assessment of treatment efficacy in CLL, complementing traditional outcome measures and accelerating access to novel drugs. Here, we provide a comprehensive review of recent major clinical trials of CLL therapy, focusing on small-molecule inhibitors and monoclonal antibody combinations that have recently emerged as the standard frontline and relapse treatment options. We explore the assessment and reporting of MRD (including novel techniques) and the challenges of standardization and provide a comprehensive review of the relevance and adequacy of MRD as a clinical trial endpoint. We further discuss the impact that MRD data have on clinical decision-making and how it can influence a patient’s experience. Finally, we evaluate how upcoming trial design and clinical practice are evolving in the face of MRD-driven outcomes.https://www.frontiersin.org/articles/10.3389/fonc.2023.1130617/fullleukemialymphocyticchronicmeasurableresidualdisease |
| spellingShingle | A. Fisher A. Fisher H. Goradia N. Martinez-Calle PEM. Patten PEM. Patten T. Munir The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials Frontiers in Oncology leukemia lymphocytic chronic measurable residual disease |
| title | The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials |
| title_full | The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials |
| title_fullStr | The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials |
| title_full_unstemmed | The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials |
| title_short | The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials |
| title_sort | evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials |
| topic | leukemia lymphocytic chronic measurable residual disease |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1130617/full |
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