Published: 28th March 2024
Minimal/measurable residual disease (MRD) refers to detecting rare cancer cells that persist in the body post-treatment, undetectable by standard tests but capable of causing relapse. In follicular lymphoma (FL), where remission is common but disease progression is slow, MRD plays a crucial role. Detecting residual cancer in the blood can guide treatment decisions, predict relapse, and facilitate early remission monitoring. While not yet standard in FL clinical practice, ongoing research explores MRD’s potential in predicting high-risk patients and enhancing testing techniques. Its integration into immunotherapy research can accelerate the transition of promising treatments into clinical practice.
Initiatives like the FLF’s Biomarker Discovery programme aim to integrate MRD into research and ultimately clinical care, reflecting a commitment to personalised treatment and improved patient outcomes through innovative research. Publications by Dr Mitchell Smith, FLF Chief Medical Officer, offer further scientific insights into MRD’s exciting role in FL management.
What is minimal/measurable residual disease?
Minimal/measurable residual disease refers to the small number of cancer cells remaining in the body after treatment. These cells, often undetectable by standard tests, such as scans and blood tests, have the potential to trigger a relapse if not eliminated. While they may not cause physical symptoms initially, their ability to multiply can lead to cancer recurrence.
What is the potential for MRD in FL treatment?
The potential uses of MRD in FL treatment are significant; While FL treatments often result in complete remissions, the slow progression of FL poses challenges in assessing treatment efficacy as one must wait for the disease to reoccur to determine how effective a treatment is. MRD presents a transformative solution by detecting small amounts of DNA or RNA shed from cancer tumour cells in the blood, enabling precise measurement of cancer levels. This is beneficial both for guiding clinical treatment decisions, improving patient outcomes and also to fast-track more promising treatments currently under research conditions.
MRD can:
• measure the effectiveness of treatment
• predict which patients are at highest risk of relapse
• confirm and monitor remissions, sooner than other tests
• identify an early return of cancer, and understand more about how and why tumour cells have returned
• identify patients who may benefit from other treatments, such as immune cell therapy
• overcome resistance challenges
• move closer towards curing FL, giving the ability to identify and eliminate every single tumour cell
• accelerate more promising effective treatments, such as immunotherapies, from research into clinical application
Understanding MRD testing
The most common methods to test for MRD in individuals with FL are flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS). These techniques involve using either bone marrow cells obtained through bone marrow aspiration (a procedure where a small sample of bone marrow is extracted) or blood samples. A positive MRD test result, known as ‘MRD positivity’, indicates the detection of post-treatment cancer cells, while a negative result, termed ‘MRD negativity,’ signifies the absence of cancer cell and is associated with longer remissions.
MRD in immunotherapy research
We have recently published blogs on the role of immunotherapy research for better and individualised treatments for FL. Applying MRD to immunotherapy trials can help answer questions on whether cancer cells are present in the body post-treatment, why, and how this resistance can be overcome. MRD coupled with the use of biomarkers in FL treatment and care holds exciting potential to accelerate the development of effective immunotherapies further, guiding personalised treatment approaches and predicting clinical outcomes. The ability to identify and eliminate every single tumour cell is another step closer towards a cure for FL.
Where are we at now?
MRD is currently being studied in clinical trials, but it is yet to be used in routine clinical practice for FL. In some countries, MRD is a standard component of patient care for certain blood cancers. Promising FL clinical trials investigating the use of MRD to predict high-risk patients at diagnosis, forecast disease transformation, and enhance techniques for assessing MRD are all current exciting areas of research.
What is the FLF doing?
The FLF has recently launched its Biomarker Discovery Programme, which is dedicated to supporting innovative research aimed at finding and validating biomarkers for FL. This research applies MRD to the context for better patient care and paves the way for applying these discoveries in clinical settings. The programme, in collaboration with the Mark Foundation for Cancer Research, is a reflection of the success of the scientific Biomarker Discovery Workshop in December 2023 and incorporates feedback from patients obtained through our recent patient survey.
Read more recent blogs on the exciting developments in immunotherapy research for better and individualised treatments for FL. For more detailed scientific insights into utilising MRD for FL, please read the publication by Dr Mitchell Smith, FLF Chief Medical Officer, “FLF’s Chief Medical Officer’s top highlights from American Society of Hematology (ASH) 2023 Annual Meeting” and other related articles here.
Additional reference:
Leukemia & Lymphoma Society. “Minimal Residual Disease.” 2022. https://www.lls.org/sites/default/files/2022-06/FS35_Minimal_Residual_Disease_2022Final.pdf
Disclaimer: This article serves to inform patients about the potential of Minimal/measurable residual disease (MRD) in follicular lymphoma research and clinical care. Patients are advised to consult with their healthcare providers for personalised treatment recommendations and considerations.
