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Multiple myeloma gammopathies

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


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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Correspondence to Luciano J. Costa.

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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).

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