# MRD-guided treatment-free intervals in myeloma

Source: https://onco.cc/ideas/idea-mrd-guided-stop-myeloma/  
OnCo record `idea-mrd-guided-stop-myeloma` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

If a patient has had no detectable myeloma for a year or more, stop maintenance and watch, restarting only if disease reappears.

## Summary

For a patient with multiple myeloma whose disease has been undetectable by MRD testing for a year or more, this idea proposes stopping maintenance and watching, restarting only if disease reappears. The rationale is that sustained MRD negativity at the most sensitive threshold predicts a very low rate of relapse, that MRD re-emergence precedes clinical relapse by months, and that indefinite lenalidomide adds toxicity, second cancers and cost. The hypothesis is that stopping after twelve months of sustained MRD negativity gives non-inferior progression-free survival with better quality of life. PERSEUS, MASTER, DRAMMATIC (SWOG S1803) and GEM2014MAIN test stopping, so it is being tested at scale; it addresses the bottlenecks of dormant cells and minimal residual disease and of trial design.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: Stopping maintenance after ≥12 months sustained MRD negativity (10⁻⁶) yields non-inferior PFS at 3 years compared with continued lenalidomide, with better quality of life.
- Rationale: MRD-negative CR at 10⁻⁶ carries ~90% 5-year PFS in modern cohorts; MRD re-emergence precedes clinical relapse by months, allowing pre-emptive restart.
- Proposed test: Randomised MRD-guided discontinuation with serial marrow/peripheral MRD and PET; PFS non-inferiority primary.
- Maturity: being-tested-at-scale

## Sources

- ClinicalTrials.gov NCT03710603: PERSEUS: https://clinicaltrials.gov/study/NCT03710603

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Newly diagnosed multiple myeloma, transplant-eligible](https://onco.cc/cancers/myeloma-transplant-eligible/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Daratumumab](https://onco.cc/drugs/daratumumab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/)
- terms: [MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)](https://onco.cc/terms/mrd-negativity-myeloma/)
- trials: [PERSEUS](https://onco.cc/trials/perseus/)
- key papers: [Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma](https://onco.cc/key-papers/paper-lenalidomide-multiple-myeloma-n-engl-j-med-2015/), [Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma](https://onco.cc/key-papers/paper-lenalidomide-multiple-myeloma-n-engl-j-med-2016/), [Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma](https://onco.cc/key-papers/paper-lenalidomide-multiple-myeloma-n-engl-j-med-2007/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)

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