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MRD Testing Evolution and Clinical Applications in Lymphoma Explored at SOHO 2024

• Next-generation sequencing and ctDNA assays have significantly advanced minimal residual disease (MRD) testing, enhancing sensitivity across lymphoma subtypes. • Clinical trials are increasingly utilizing MRD status to guide lymphoma therapy, influencing treatment escalation, de-escalation, consolidation, and therapy initiation/cessation. • Research is paving the way for personalized lymphoma treatments using ctDNA assays, which offer insights into tumor biology and may transform clinical decision-making.

Advancements in circulating tumor DNA (ctDNA) assays and next-generation sequencing are transforming minimal residual disease (MRD) testing in lymphoma, offering new avenues for personalized treatment strategies. Reid Merryman, MD, clinical investigator and assistant professor at Dana Farber Cancer Institute, discussed these developments at the SOHO 2024 Annual Meeting, highlighting the evolution and clinical applications of MRD testing.

Evolution of MRD Testing

Merryman explained that while MRD testing isn't new in lymphoma, traditional methods like flow cytometry and PCR were limited to specific subtypes. The advent of next-generation sequencing has enabled ctDNA tracking across all lymphoma subtypes, enhancing the sensitivity of these assays. Early methods tracked one or a few tumor reporters, while newer panel-based assays and whole-genome sequencing approaches can track hundreds or even thousands, significantly improving sensitivity.

MRD-Guided Therapy in Clinical Trials

Currently, numerous trials are tracking MRD by collecting plasma samples to observe changes with treatment. Some trials are now using MRD to guide therapies, such as escalating or de-escalating treatment based on early MRD status, or guiding consolidation strategies. For example, a phase 3 trial in mantle cell lymphoma uses MRD status to guide consolidation with transplant. Trials in large cell lymphoma are also exploring intensification of frontline treatment based on interim MRD status.

Broader Applications of ctDNA

Beyond MRD enumeration, ctDNA can provide insights into tumor biology. Research is exploring the identification of lymphoma subgroups based on ctDNA, including LymphGen classification in diffuse large B cell lymphoma. Similar results have been observed in Hodgkin lymphoma, which is challenging to analyze using tissue samples due to the rarity of tumor cells. Gene expression can also be inferred from ctDNA, potentially aiding in the identification of double-hit lymphoma or transformation of indolent lymphomas.

Significance Across Lymphoma Subtypes

While the most data is currently available for diffuse large B cell lymphoma, research is expanding to other subtypes, including Hodgkin lymphoma and follicular lymphoma. Merryman noted that different lymphoma subtypes have distinct biologies, necessitating tailored tests for accurate assessment.

Challenges and Future Directions

Despite the progress, challenges remain in standardizing MRD assessment across different centers due to the variety of assays in use and development. To integrate MRD testing into clinical practice, a consensus on a single assay for specific clinical scenarios is needed, guided by ongoing clinical trials. The key takeaway from Merryman's presentation is that unprecedented advances in ctDNA assays over the past decade are now paving the way for personalized therapy and improved outcomes for lymphoma patients.
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Reference News

[1]
The Evolution and Clinical Applications of MRD Testing in Lymphoma - Pharmacy Times
pharmacytimes.com · Sep 6, 2024

Reid Merryman, MD, discussed the evolution of minimal residual disease (MRD) testing in lymphoma, focusing on the use of...

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