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. 2024 Oct 7;14(1):170.
doi: 10.1038/s41408-024-01156-x.

Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)

Benjamin A Derman  1 , Ajay Major  2 , Jennifer Cooperrider  3 , Ken Jiang  3 , Aubrianna Ramsland  3 , Theodore Karrison  4 , Tadeusz Kubicki  3 , Andrzej J Jakubowiak  3
Affiliations

Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)

Benjamin A Derman et al. Blood Cancer J. .

Abstract

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10-5, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytometry (limit of detection [LoD] 10-5), and BM clonoSEQ (LoD 10-6). BM aspirates enriched for CD138+ cells were analyzed by clonoSEQ to achieve MRD 10-7 sensitivity. We evaluated the incidence of disease resurgence and progression-free survival (PFS), stratified by 10-7 status. Forty-seven patients discontinued maintenance after a median of 36 months. Baseline MRD ≥ 10-7 was observed in 19% (9/47). The median follow-up post-discontinuation was 30 months. Disease resurgence (MRD 10 ≥ -6) occurred in 11 patients, including 5 disease progressions. One patient died from a second cancer. The estimated 3-year cumulative incidence of disease resurgence was 20% for patients with baseline MRD < 10-7 compared to 75% for MRD ≥ 10-7 (HR 7.8, 95% CI 2.2-27.6, p = 0.001). Baseline MRD ≥ 10-7 was associated with inferior PFS compared to MRD < 10-7 (HR 10.1, 95% CI 1.6-62.3; 3-year PFS 49% vs 92%). Maintenance discontinuation in patients with MM and MRD < 10-6 led to low rates of disease resurgence. MRD < 10-7 may be a superior cessation threshold, requiring further validation.

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Conflict of interest statement

B.A.D. declares consultancy for Johnson & Johnson, Sanofi, Canopy, and Cota Inc.; independent clinical trial reviewer for BMS; research funding from GSK and Amgen. A.M., J.C., K.J., A.R., Th.K., and Ta.K. have nothing to disclose. A.J.J. declares honoraria and advisory board fees from Abbvie, Amgen, Bristol-Myers Squibb/Celgene, GlaxoSmithKline, Gracell, Janssen, and Sanofi.

Figures

Fig. 1
Fig. 1. Enrollment and evaluable patients.
A CONSORT diagram of patients assessed for eligibility and subsequently enrolled.
Fig. 2
Fig. 2. MRD-free survival and progression-free survival for all patients.
MRD-free survival (MRD-FS; red) refers to patients free of MRD 10−6 resurgence, progression, or death. Progression-free survival (PFS; blue) refers to patients free of progression or death.
Fig. 3
Fig. 3. Outcomes By MRD 10-7 Status.
A MRD-free survival (MRD-FS) and B progression-free survival (PFS) stratified by MRD 10−7 status at baseline. MRD-FS refers to patients free of MRD 10−6 resurgence, progression, or death.
Fig. 4
Fig. 4. Longitudinal mean score changes from baseline in selected Patient Reported Outcome Domains from the EORTC QLQ-C30 Instrument.
MID minimally important difference.
See this image and copyright information in PMC

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