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. 2021 Oct 1;27(19):5195-5212.
doi: 10.1158/1078-0432.CCR-21-1059.

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Kenneth C Anderson  1 , Daniel Auclair  2 , Stacey J Adam  3 , Amit Agarwal  4 , Melissa Anderson  5 , Hervé Avet-Loiseau  6 , Mark Bustoros  7 , Jessica Chapman  8 , Dana E Connors  3 , Ajeeta Dash  5 , Alessandra Di Bacco  5 , Ling Du  9 , Thierry Facon  10 , Juan Flores-Montero  11 , Francesca Gay  12 , Irene M Ghobrial  13 , Nicole J Gormley  14 , Ira Gupta  9 , Howard Higley  15 , Jens Hillengass  16 , Bindu Kanapuru  14 , Dickran Kazandjian  17 , Gary J Kelloff  18 , Ilan R Kirsch  19 , Brandon Kremer  9 , Ola Landgren  17 , Elizabeth Lightbody  13 , Oliver C Lomas  13 , Sagar Lonial  20 , María-Victoria Mateos  21 , Rocio Montes de Oca  9 , Lata Mukundan  15 , Nikhil C Munshi  22 , Elizabeth K O'Donnell  23 , Alberto Orfao  11 , Bruno Paiva  24 , Reshma Patel  25 , Trevor J Pugh  26 , Karthik Ramasamy  27 , Jill Ray  28 , Mikhail Roshal  8 , Jeremy A Ross  29 , Caroline C Sigman  15 , Katie L Thoren  8 , Suzanne Trudel  26 , Gary Ulaner  30 , Nancy Valente  28 , Brendan M Weiss  25 , Elena Zamagni  31 , Shaji K Kumar  32
Affiliations

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Kenneth C Anderson et al. Clin Cancer Res. .

Abstract

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy-based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid-based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.

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Figures

Figure 1. Clinical Case 1—Use of MRD in a patient with smoldering myeloma.
Figure 1.
Clinical Case 1—Use of MRD in a patient with smoldering myeloma.
Figure 2. Clinical Case 2—Use of MRD in a newly diagnosed transplant-eligible normal-risk patient.
Figure 2.
Clinical Case 2—Use of MRD in a newly diagnosed transplant-eligible normal-risk patient.
Figure 3. Clinical Case 3—Use of MRD in a newly diagnosed transplant-eligible high-risk patient.
Figure 3.
Clinical Case 3—Use of MRD in a newly diagnosed transplant-eligible high-risk patient.
Figure 4. Clinical Case 4—Use of MRD in a newly diagnosed transplant-ineligible patient.
Figure 4.
Clinical Case 4—Use of MRD in a newly diagnosed transplant-ineligible patient.
Figure 5. Clinical Case 5—Use of MRD for treatment-free monitoring.
Figure 5.
Clinical Case 5—Use of MRD for treatment-free monitoring.
Figure 6. Clinical Case 6—Use of MRD in a patient with relapsed refractory myeloma.
Figure 6.
Clinical Case 6—Use of MRD in a patient with relapsed refractory myeloma.
See this image and copyright information in PMC

References

    1. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. . International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17:e328–e46. - PubMed
    1. Anderson KC, Auclair D, Kelloff GJ, Sigman CC, Avet-Loiseau H, Farrell AT, et al. . The role of minimal residual disease testing in myeloma treatment selection and drug development: current value and future applications. Clin Cancer Res 2017;23:3980–93. - PubMed
    1. Munshi NC, Avet-Loiseau H, Anderson KC, Neri P, Paiva B, Samur M, 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;4:5988–99. - PMC - PubMed
    1. Martinez-Lopez J, Wong SW, Shah N, Bahri N, Zhou K, Sheng Y, et al. . Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma. Blood Adv 2020;4:3295–301. - PMC - PubMed
    1. Flores-Montero J, Sanoja L, Pérez JJ, Pojero F, Puig N, Vidriales MB, et al. . Plasma cell disorders. In: Detrick B, Schmitz JL, Hamilton RG, editors. Manual of molecular and clinical laboratory immunology. Washington, DC: ASM Press; 2016. p. 235–50.

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