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This trial was the first to prospectively assess molecular response and the impact on outcomes for 400 patients. The median progression\u2010free survival (PFS) and overall survival (OS) for CMD were 3\u00b76 and 14\u00b76\u00a0years vs. 3\u00b70 and 15\u00b77\u00a0years for FMD, respectively. Estimates for Restricted Mean Survival Time (RMST) suggested no difference in PFS or OS. For the whole cohort there was a highly significant difference in survival by POD24, with a median OS from a risk\u2010defining event of 3\u00b79\u00a0years compared to 13\u00b77\u00a0years for all others (RMST <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001). Molecular remission was achieved in 25\/46 patients (54\u00b73%) in the CMD arm and 20\/41 (48\u00b78%) in the FMD arm (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b76). Molecular negativity resulted in median PFS of 5\u00b76\u00a0years vs. 2\u00b73\u00a0years for molecularly positive (log\u2010rank <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) and median OS not reached <jats:italic>versus<\/jats:italic> 12\u00b75\u00a0years (log\u2010rank <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b701). No cases of progression occurred in minimal residual disease (MRD) negative patients after six years of follow\u2010up. Although there was no difference in outcomes between arms, this is the first prospective study to report MRD negativity resulting in significantly improved OS.<\/jats:p>","DOI":"10.1111\/bjh.16555","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T19:12:33Z","timestamp":1583781153000},"page":"545-554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) <i>versus<\/i> fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival"],"prefix":"10.1111","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-1036","authenticated-orcid":false,"given":"Mark J.","family":"Bishton","sequence":"first","affiliation":[{"name":"Clinical Haematology Nottingham City Hospital Nottingham 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