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Telomere length predicts for outcome to FCR chemotherapy in CLL

Norris, Kevin, Hillmen, Peter, Rawstron, Andrew, Hills, Robert, Baird, Duncan M., Fegan, Christopher D. and Pepper, Chris 2019. Telomere length predicts for outcome to FCR chemotherapy in CLL. Leukemia 33 , pp. 1953-1963. 10.1038/s41375-019-0389-9

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Abstract

We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could predict for outcome to fludarabine, cyclophosphamide, rituximab (FCR)-based treatment using samples collected from two concurrent phase II studies, ARCTIC and ADMIRE (n = 260). In univariate analysis, patients with TL-IFR had reduced progression-free survival (PFS) (P < 0.0001; HR = 2.17) and shorter overall survival (OS) (P = 0.0002; HR = 2.44). Bifurcation of the IGHV-mutated and unmutated subsets according to telomere length revealed that patients with TL-IFR in each subset had shorter PFS (HR = 4.35 and HR = 1.48, respectively) and shorter OS (HR = 3.81 and HR = 2.18, respectively). In addition, the OS of the TL-OFR and TL-IFR subsets were not significantly altered by IGHV mutation status (P = 0.61; HR = 1.24 and P = 0.41; HR = 1.47, respectively). In multivariate modeling, telomere length was the dominant co-variable for PFS (P = 0.0002; HR = 1.85) and OS (P = 0.05; HR = 1.61). Taken together, our data suggest that HT-STELA is a powerful predictor of outcome to FCR-based treatment and could be used to inform the design of future risk-adapted clinical trials.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Springer Nature
ISSN: 0887-6924
Date of First Compliant Deposit: 1 February 2019
Date of Acceptance: 28 December 2018
Last Modified: 03 Sep 2019 12:46
URI: http://orca.cf.ac.uk/id/eprint/119085

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