# MRD-guided treatment duration in CLL

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

## TL;DR

Instead of a fixed 12 or 15 months, stop each patient's therapy when their blood shows no detectable leukaemia, and restart if it returns.

## Summary

The idea is to stop each chronic lymphocytic leukaemia patient's fixed-duration therapy when an NGS-based MRD assay such as clonoSEQ shows no detectable leukaemia in blood, and to restart at relapse, rather than treating everyone for a fixed twelve or fifteen months. Undetectable MRD at the end of treatment is the strongest predictor of progression-free survival, and patients with mutated IGHV reach it earlier and stay in remission longer. The hypothesis is non-inferior progression-free survival with a third less drug exposure. CAPTIVATE's MRD-guided cohort and FLAIR's MRD-directed arm suggest this is feasible, SPRUCE-TN with sonrotoclax and zanubrutinib formalises it, and retreatment at relapse works in most patients; the idea is being tested at scale.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: MRD-guided duration (stop at confirmed uMRD ≤10^-4, or continue to a maximum) yields PFS non-inferior to fixed 12-15 months while reducing drug exposure by a third.
- Rationale: uMRD at end of treatment is the strongest predictor of PFS; IGHV-mutated patients reach uMRD earlier and stay in remission longer.
- Proposed test: Randomised MRD-guided vs fixed duration with clonoSEQ monitoring every 3 months; primary endpoint PFS, secondary exposure and cost.
- Maturity: being-tested-at-scale

## Sources

- ClinicalTrials.gov NCT02910583: CAPTIVATE: https://clinicaltrials.gov/study/NCT02910583
- ClinicalTrials.gov NCT06073821: CELESTIAL-TNCLL: https://clinicaltrials.gov/study/NCT06073821

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/)
- technologies: [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/)
- drugs: [Sonrotoclax](https://onco.cc/drugs/sonrotoclax/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- terms: [IGHV mutational status](https://onco.cc/terms/ighv-status/), [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/)
- trials: [CAPTIVATE](https://onco.cc/trials/captivate/), [CELESTIAL-TNCLL](https://onco.cc/trials/celestial-tncll/)
- key papers: [Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia](https://onco.cc/key-papers/paper-zanubrutinib-cll-n-engl-j-med-2023/), [Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial](https://onco.cc/key-papers/paper-zanubrutinib-cll-lancet-oncol-2022/), [Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial](https://onco.cc/key-papers/paper-zanubrutinib-cll-lancet-haematol-2021/)

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