Dr Merryman on the Evolution of MRD Assays in Lymphoma

Reid Merryman, MD, instructor in medicine, Harvard Medical School; attending physician, Dana-Farber Cancer Institute, discusses the evolution of minimal residual disease (MRD) assays in lymphoma, highlighting information shared at the 2024 SOHO Annual Meeting.

Merryman begins by outlining the 3 main categories of MRD assays used to monitor minimal disease presence and guide treatment: immunoglobulin high-throughput sequencing (IgHTS), panel-based assays, and emerging assays like PhasED-seq and MAESTRO.

IgHTS assays, such as clonoSEQ, are the least sensitive of these assays, he expands. They track 1 to 5 tumor reporters and use next-generation sequencing (NGS) to identify unique disease-associated immunoglobulin (Ig) sequences, including IgH, IgK, and IgL rearrangements and IgH-BCL1/2 translocations, Merryman explains. Studies have shown that circulating tumor DNA (ctDNA) assessments with this method correlate with disease burden and dynamic changes over time, linking them to PET responses and progression-free survival in diffuse B-cell lymphoma (DLBCL).

Panel-based assays, such as CAPP-seq, offer greater sensitivity by tracking dozens of tumor-specific mutations, Merryman continues. These panels are disease-specific, facilitating the identification of mutations in ctDNA at a higher frequency than IgHTS, particularly at relapse, he says. CAPP-seq assays improve the likelihood of detecting a tumor genotype, ctDNA prior to treatment, and ctDNA during relapse, enhancing early detection capabilities.

The most recent assays developed in this space include PhasED-seq and whole-genome sequencing-based assays like MAESTRO, which offer the highest sensitivity, Merryman details. PhasED-seq tracks hundreds to thousands of tumor reporters by exploiting phase variants. MAESTRO assays, using allele-specific probes and Duplex Sequencing, enrich thousands of prespecified mutations, requiring fewer sequencing reads for detection. These approaches significantly improve the ability to detect MRD and track disease progression, Merryman emphasizes.

With increased sensitivity of these MRD assays, excitement continues to generate around their potential to guide therapy in DLBCL, Merryman notes. Early trials are now using MRD results to adjust therapy in real-time, and frontline treatment intensification is being informed by interim MRD status, potentially improving outcomes by customizing care based on individual patient response, he concludes.