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Utility of Measurable Residual Disease (MRD) Assessment in Mantle Cell Lymphoma

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Opinion statement

Mantle cell lymphoma (MCL) treatment advances have significantly improved disease-free remission, with greater focus in clinical trials being placed on measurable residual disease (MRD) as a marker of subclinical disease assessment. While this concept is used extensively in other haematological neoplasms, there is yet to be a consensus on the threshold for MRD in MCL that demonstrates prognostic and therapeutic significance, and in this context has yet to reach routine clinical practice. The historical long-term method for MCL MRD assessment has been real-time quantitative polymerase chain reaction (PCR), targeting the clonal immunoglobulin heavy locus (IGH) rearrangement or the IGH::CCND1 translocation rearrangement. A significant problem at present relates to identifying alternative assays for patients who do not have a suitable molecular target by this method. This article reviews existing techniques used in MRD assessment for MCL and describes novel methods which may overcome existing limitations, including next-generation sequencing modalities. The use of circulating tumour DNA is explored, with techniques such as CAPP-Seq and PhasED-Seq demonstrating promise in B-lymphoproliferative disorders, though application in MCL requires further study. The other aspect of practice using MRD is identifying therapeutic options which can address a subclinical molecular relapse. Developing suitable interventions that can alter the disease trajectory based on longitudinal MRD kinetics are needed to justify its incorporation into standard care.

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Authors and Affiliations

  1. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    Simon Wu MBBS, Piers Blombery MBBS PhD & David Westerman MBBS

  2. Department of Clinical Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    Piers Blombery MBBS PhD & David Westerman MBBS

  3. Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia

    Piers Blombery MBBS PhD & David Westerman MBBS

  4. Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia

    Constantine S. Tam MBBS MD

  5. Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia

    Constantine S. Tam MBBS MD

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Correspondence to Simon Wu MBBS.

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Simon Wu declares that he has no conflict of interest. Piers Blombery has received honoraria from Adaptive Biotechnologies, AstraZeneca and Servier. David Westerman has served as a consultant for Pfizer Australia. Constantine Tam has served as a consultant for AbbVie and AstraZeneca, and has received honoraria from AbbVie, BeiGene and Janssen.

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Supplemental Table 1: MRD in previous studies. Adapted from Jung et al. 2020 [34] and Ladetto et al. 2020[35] with updates. APO: doxorubicin, prednisolone, vincristine. ASCT: autologous stem cell transplant. BM: bone marrow. BR: bendamustine, rituximab. COP: cyclophosphamide, vincristine, prednisolone. DA-EPOCH-R: dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab. DHAP: dexamethasone, cytarabine, cisplatin. EAR: etoposide, cytarabine, rituximab. EFS: event free survival. FL: follicular lymphoma. IGH: Immunoglobulin heavy chain. MCL: mantle cell lymphoma. MRD: measurable residual disease. MRD-: MRD negative. MRD+: MRD positive. MTX: methotrexate. N/A: data not available. NGS-IGH: next-generation sequencing of IGH clonotype. OS: overall survival. PB: peripheral blood. PFS: progression free survival. PM: prednimustine, mitoxantrone. RC: rituximab, cytarabine. R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone. RT-qPCR: real-time quantitative polymerase chain reaction. R-VAD+C: rituximab, vincristine, doxorubicin, dexamethasone, chlorambucil. SLL: small lymphocytic lymphoma. V: bortezomib. Z: 90Y-ibritumomab-tiuxetan. (DOCX 29.4 KB)

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Wu, S., Blombery, P., Westerman, D. et al. Utility of Measurable Residual Disease (MRD) Assessment in Mantle Cell Lymphoma. Curr. Treat. Options in Oncol. 24, 929–947 (2023). https://doi.org/10.1007/s11864-023-01102-2

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