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Frequently Asked Questions About MRD

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What is MRD?

MRD describes the low level of malignant cells that persist in the bone marrow after treatment but cannot be detected with conventional outcome measures and which eventually lead to relapse. A patient who is MRD negative at 10-5 has achieved clinical remission with the absence of aberrant clonal cells by NGF or NGS per at least 100,000 nucleated cells.1,2

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How does MRD negativity compare with other response measures?

Studies have shown MRD- to be an important measurement for depth of response, acting as a surrogate marker for longer PFS and OS. Studies have also demonstrated that even among patients who achieve CR, remaining MRD+ may be associated with poorer prognosis.1,3,4

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Has MRD negativity been studied in clinical trials?

MRD- has been studied in clinical trials evaluating response rates in NDMM and RRMM. MRD- has been associated with significantly improved PFS and OS.3

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Should I consider MRD when making treatment decisions?

The use of MRD- to inform treatment decisions is under investigation, including whether maintenance or continuous therapy in MRD- patients can be stopped or whether treatment needs to be changed in MRD+ patients, especially in high-risk multiple myeloma.5

Further clinical investigations in multiple myeloma will help clarify the role of MRD in making treatment decisions.5

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CR=complete response; MRD=minimal residual disease; MRD-=minimal residual disease negative/negativity; MRD+=minimal residual disease positive/positivity; NDMM=newly diagnosed multiple myeloma; NGF=next-generation flow; NGS=next-generation sequencing; OS=overall survival; PFS=progression-free survival; RRMM=relapsed and/or refractory multiple myeloma.

REFERENCES: 1. Kostopoulos IV, Ntanasis-Stathopoulos I, Gavriatopoulou M, Tsitsilonis OE, Terpos E. Minimal residual disease in multiple myeloma: current landscape and future applications with immunotherapeutic approaches. Front Oncol. 2020;10:860. 2. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-e346. 3. Munshi NC, Avet-Loiseau H, Anderson KC, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4(23):5988-5999. 4. Lahuerta JJ, Paiva B, Vidriales MB, et al. Depth of response in multiple myeloma: a pooled analysis of three PETHEMA/GEM clinical trials. J Clin Oncol. 2017;35(25):2900-2910. 5. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309-322.