{"entity":{"id":"idea-mrd-guided-stop-cll","kind":"idea","name":"MRD-guided treatment duration in CLL","aka":[],"tldr":"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.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02910583: CAPTIVATE","url":"https://clinicaltrials.gov/study/NCT02910583"},{"label":"ClinicalTrials.gov NCT06073821: CELESTIAL-TNCLL","url":"https://clinicaltrials.gov/study/NCT06073821"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":["ngs-mrd-clonoseq"],"targets":[],"drugs":["venetoclax","zanubrutinib","sonrotoclax"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd-negative-cr","ighv-status"],"trials":["captivate","celestial-tncll"],"people":[],"bottlenecks":[],"keyPapers":["paper-zanubrutinib-cll-n-engl-j-med-2023","paper-zanubrutinib-cll-lancet-oncol-2022","paper-zanubrutinib-cll-lancet-haematol-2021"],"journals":[],"dependsOn":[],"notes":[],"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.","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"},"route":"/ideas/idea-mrd-guided-stop-cll/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"}],"technology":[{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"}],"drug":[{"id":"sonrotoclax","kind":"drug","name":"Sonrotoclax","route":"/drugs/sonrotoclax/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"term":[{"id":"ighv-status","kind":"term","name":"IGHV mutational status","route":"/terms/ighv-status/"},{"id":"mrd-negative-cr","kind":"term","name":"MRD-negative complete remission","route":"/terms/mrd-negative-cr/"}],"trial":[{"id":"captivate","kind":"trial","name":"CAPTIVATE","route":"/trials/captivate/"},{"id":"celestial-tncll","kind":"trial","name":"CELESTIAL-TNCLL","route":"/trials/celestial-tncll/"}],"paper":[{"id":"paper-zanubrutinib-cll-n-engl-j-med-2023","kind":"paper","name":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","route":"/key-papers/paper-zanubrutinib-cll-n-engl-j-med-2023/"},{"id":"paper-zanubrutinib-cll-lancet-oncol-2022","kind":"paper","name":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial","route":"/key-papers/paper-zanubrutinib-cll-lancet-oncol-2022/"},{"id":"paper-zanubrutinib-cll-lancet-haematol-2021","kind":"paper","name":"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","route":"/key-papers/paper-zanubrutinib-cll-lancet-haematol-2021/"}]}}