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Multiple myeloma gammopathies

International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials

Leukemia volume 35, pages 18–30 (2021)Cite this article

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Abstract

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

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Fig. 1: Representation of appropriate calculation and reporting of MRD following intention-to-treat principle.

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Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Luciano J. Costa & Susan Bal

  2. Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA

    Benjamin A. Derman & Andrzej J. Jakubowiak

  3. Department of Medicine, Stanford University, Stanford, CA, USA

    Surbhi Sidana

  4. Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Saurabh Chhabra, Marcelo Pasquini & Parameswaran Hari

  5. Division of Hematology and Medical Oncology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA

    Rebecca Silbermann

  6. Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA

    Jing C. Ye

  7. Haematology & Myeloma Studies, Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK

    Gordon Cook

  8. Division of Hematology & Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Robert F. Cornell

  9. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Sarah A. Holstein

  10. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    Qian Shi

  11. Independent Patient Advocate, Omaha, NE, USA

    James Omel

  12. Carbone Cancer Center, University of Wisconsin, Madison, WI, USA

    Natalie S. Callander

  13. National University Health System, Singapore, Singapore

    Wee Joo Chng

  14. Clinica São Germano, São Paulo, Brazil

    Vania Hungria

  15. Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Angelo Maiolino

  16. University of Pennsylvania, Philadelphia, PA, USA

    Edward Stadtmauer

  17. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Sergio Giralt

  18. New York University Langone Health, New York, NY, USA

    Gareth J. Morgan

  19. City of Hope, Duarte, CA, USA

    Amrita Krishnan

  20. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

    Graham H. Jackson

  21. Hôpital Saint-Antoine, Paris, France

    Mohamad Mohty

  22. Department of Haematology, University Hospital of Salamanca, Salamanca, Spain

    Maria Victoria Mateos

  23. School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Meletious A. Dimopoulos

  24. Service des Maladies du Sang, Centre Hospitalier Universitaire (CHU) Lille, University of Lille, Lille, France

    Thierry Facon

  25. Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, VA, Australia

    Andrew Spencer

  26. Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada Instituto de Investigacion Sanitaria de Navarra, Pamplona, Spain

    Jesus San Miguel & Bruno Paiva

  27. Plasma Cell Disorders Division, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Charlotte, NC, USA

    Saad Z. Usmani

  28. Department of Hematology, Université de Lille, CHU, Lille, France

    Salomon Manier

  29. Roswell Park Cancer Institute, Buffalo, NY, USA

    Phillip McCarthy

  30. Department of Hematology, Mayo Clinic Rochester, Rochester, MN, USA

    Shaji Kumar

  31. Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy

    Francesca Gay

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  1. Luciano J. Costa
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  2. Benjamin A. Derman
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Corresponding author

Correspondence to Luciano J. Costa.

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Conflict of interest

LC: Honoraria (Amgen, Bristol-Myers-Squibb, AbbVie), Research Funding (Amgen, Bristol-Myers-Squibb, Janssen); RS: Honoraria (Janssen); VH: Honoraria (Janssen, AbbVie, Amgen, Bristol-Myers-Squibb, Celgene, Takeda); W-JC: Honoraria (Takeda); ES: Honoraria (Celgene, Takeda, Novartis, Teva, Janssen, Amgen, Sanofi); SG: Honoraria (Celgene, Takeda, Amgen, Jazz Pharmaceuticals, Sanofi, Sanofi, Janssen), Research Funding (Celgene, Takeda, Miltenyi Biotec, Johnson & Johnson, Amgen); AJJ: Honoraria (Amgen, Bristol-Myers-Squibb, Janssen, Takeda, Skyline DX), Consultancy (Abbvie); GJM: Honoraria (Celgene, Bristol-Myers-Squibb, Novartis, Roche, Genentech, Takeda, Amgen, Karyopharm, Sanofi, GlaxoSmithKline, Janssen); AK: Ownership Interest (Celgene, Kite Pharma), Honoraria (Celgene, Onyx, Janssen, Takeda, Kite Pharma, Seattle Genetics), Research Funding (Celgene, Takeda); GHJ: Honoraria (Roche, Amgen, Janssen); MM: Honoraria (Janssen, Sanofi, Jazz Pharmaceuticals, Celgene, Bristol-Myers Squibb, Takeda, Amgen, Roche); MM: Honoraria (Janssen, Sanofi, Jazz Pharmaceuticals, Celgene, Bristol-Myers Squibb, Takeda, Amgen) Research support (Roche); MVV: Honoraria (Janssen, Celgene, Amgen, Takeda, AbbvVie, GlaxoSmithKline, Adaptive, Edo-Mundipharma, PharmaMar); MAD: Honoraria (Amgen, Janssen, Takeda, Celgene, Bristol-Myers Squibb); TF: Honoraria (Celgene, Janssen, Takeda, Amgen, Sanofi, Karyopharm, Oncopeptides, Roche); AS: Honoraria (Takeda, Celgene, Janssen, Amgen), Research funding (Takeda, Celgene, Janssen, GlaxoSmithKline); JSM: Honoraria (Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche); PH: Honoraria (Takeda, Prothena, Pfizer), Research funding (Takeda); SU: Honoraria (Bristol-Myers-Squibb, Amgen, Takeda, Sanofi, Janssen), Research funding (Onyx, Janssen, Sanofi, Array BioPharma, Pharmacyclics, Takeda, Celgene, Bristol-Myers Squibb); PM: Honoraria (Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Sanofi, Janssen, The Binding Site), Research support (Celgene); SK: Honoraria (AbbVie, Celgene, Kite Pharma). FG: Honoraria (Takeda, Amgen, Celgene, Janssen, Bristol-Myers-Squibb, Seattle Genetics, Roche). BP: Honoraria (Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Takeda, Sanofi), Research funding (Celgene, Janssen-Cilag, Sanofi, Takeda).

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Costa, L.J., Derman, B.A., Bal, S. et al. International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials. Leukemia 35, 18–30 (2021). https://doi.org/10.1038/s41375-020-01012-4

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