The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival

Bishton, Mark J.; Rule, Simon; Wilson, William; Turner, Deborah; Patmore, Russell; Clifton‐Hadley, Laura; McMillan, Andrew; Lush, Richard; Haynes, Andrew

Abstract

We present a long-term follow-up of the UK chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced, symptomatic follicular lymphoma (FL). This trial was the first to prospectively assess molecular response and the impact on outcomes for 400 patients. The median progression-free survival (PFS) and overall survival (OS) for CMD were 3·6 and 14·6years vs. 3·0 and 15·7years 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-defining event of 3·9years compared to 13·7years for all others (RMST P<0·001). Molecular remission was achieved in 25/46 patients (54·3%) in the CMD arm and 20/41 (48·8%) in the FMD arm (P=0·6). Molecular negativity resulted in median PFS of 5·6years vs. 2·3years for molecularly positive (log-rank P<0·001) and median OS not reached versus 12·5years (log-rank P<0·01). No cases of progression occurred in minimal residual disease (MRD) negative patients after six years of follow-up. Although there was no difference in outcomes between arms, this is the first prospective study to report MRD negativity resulting in significantly improved OS.

Citation

Bishton, M. J., Rule, S., Wilson, W., Turner, D., Patmore, R., Clifton‐Hadley, L., …Haynes, A. (2020). The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival. British Journal of Haematology, 190(4), 545-554. https://doi.org/10.1111/bjh.16555

• Journal Article Type: Article
• Acceptance Date: Feb 5, 2020
• Online Publication Date: Mar 9, 2020
• Publication Date: 2020-08
• Deposit Date: Dec 15, 2022
• Journal: British Journal of Haematology
• Print ISSN: 0007-1048
• Electronic ISSN: 1365-2141
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 190
• Issue: 4
• Pages: 545-554
• DOI: https://doi.org/10.1111/bjh.16555
• Keywords: Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/14322675
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/bjh.16555