Efforts to identify prognostic biomarkers in mantle cell lymphoma (MCL) are ongoing, but one of the most promising is measurable residual disease (MRD). MRD is well established in several cancers, and recent clinical trial data suggest that MRD also has prognostic value in MCL.

Currently, there is no universally accepted method for MRD assessment. In the past, multiparameter flow cytometry was commonly used, but this technique has limited sensitivity. The gold standard, real-time, quantitative polymerase chain reaction (qPCR) is currently the most commonly used method, but it is labor intensive and can only be used in patients whose tumor has an identifiable molecular alteration. The field is now evaluating next-generation sequencing (NGS) methods of MRD detection for MCL, some of which are US Food and Drug Administration (FDA) cleared for other cancers. However, like qPCR, NGS requires the identification of a molecular alteration in a pretreatment tissue sample. Often, qPCR and some NGS methods are geared to detect IGH gene rearrangements, but approximately 10% to 15% of patients with MCL do not have those alterations.

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Newer NGS methods can be done without a pretreatment sample and are noteworthy for using circulating tumor DNA. These include cancer personalized profiling by deep sequencing (CAPP-Seq) and, the most sensitive MRD detection method, phased variant enrichment and detection sequencing (PhasED-Seq), which was developed by the same group that developed CAPP-Seq. There is also anchored multiplex PCR to enrich the number of target sequences for NGS. These technologies have not received FDA clearance.

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The meaning of MRD status in MCL has been studied in a number of clinical trials. In general, studies have found that MRD negativity points to a longer progression-free survival (PFS) and overall survival (OS). In the LyMA trial, patients underwent chemoimmunotherapy followed by autologous stem cell transplant (ASCT) and either rituximab maintenance or observation. In the ancillary LyMA-MRD project, MRD status prior to ASCT was predictive of PFS and OS; patients who received rituximab maintenance had improved PFS and OS regardless of their MRD status before or after transplant.

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A similar Italian study evaluating lenalidomide maintenance vs observation after ASCT assessed MRD longitudinally and found that when MRD was evaluated soon after ASCT, MRD-positive and -negative patients had a similar PFS. However, when MRD was assessed 6 months after ASCT, MRD status was prognostic.

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Finally, in the European Mantle Cell Lymphoma Elderly trial, researchers evaluated whether MRD status at the end of induction influenced the efficacy of rituximab maintenance therapy. The results confirmed the importance of rituximab maintenance and found that treatment de-escalation cannot be recommended for patients with MRD-negative MCL.