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Title: Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial.
Austin Authors: Kühnl, A;Cunningham, D;Counsell, Nicholas;Hawkes, Eliza A ;Qian, W;Smith, P;Chadwick, N;Lawrie, A;Mouncey, P;Jack, A;Pocock, C;Ardeshna, Kirit M;Radford, J;McMillan, A;Davies, J;Turner, D;Kruger, A;Johnson, P W;Gambell, J;Rosenwald, A;Ott, G;Horn, H;Ziepert, M;Pfreundschuh, M;Linch, D
Affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey
Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
Olivia-Newton John Cancer Research & Wellness Centre, Heidelberg, Victoria, Australia
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge
HMDS, St James's Institute of Oncology, Leeds
East Kent Hospitals, Canterbury
Department of Hematology, University College London, London
Mount Vernon Cancer Centre, Northwood
Department of Medical Oncology, University of Manchester and the Christie NHS Foundation Trust, Manchester
Department of Hematology, Nottingham City Hospital, Nottingham
Western General Hospital, Edinburgh
Department of Hematology, Torbay Hospital, Torquay
Royal Cornwall Hospital, Truro
Cancer Research UK Center, University of Southampton, Southampton, UK
Institute of Pathology, Würzburg University, Würzburg
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tübingen, Stuttgart
Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig
Department of Medicine, Saarland University Medical School, Homburg/Saar, Germany
Issue Date: 1-Jul-2017
Publication information: Annals of oncology 2017; 28(7): 1540-1546
Abstract: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up. Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).
DOI: 10.1093/annonc/mdx128
Journal: Annals of oncology : official journal of the European Society for Medical Oncology
PubMed URL: 28398499
Type: Journal Article
Subjects: MYC
diffuse large B-cell lymphoma
double-hit lymphoma
Appears in Collections:Journal articles

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