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.
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Date
2017-07Author
Kühnl, A
Cunningham, D
Counsell, N
Hawkes, EA
Qian, W
Smith, P
Chadwick, N
Lawrie, A
Mouncey, P
Jack, A
Pocock, C
Ardeshna, KM
Radford, J
McMillan, A
Davies, J
Turner, D
Kruger, A
Johnson, PW
Gambell, J
Rosenwald, A
Ott, G
Horn, H
Ziepert, M
Pfreundschuh, M
Linch, D
Type
Journal Article
Metadata
Show full item recordAbstract
Background 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.Patients and methods 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.Results 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.Conclusions 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.Trial numbers ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).
Collections
Subject
Humans
Cyclophosphamide
Vincristine
Doxorubicin
Prednisone
Proto-Oncogene Proteins c-myc
Proto-Oncogene Proteins c-bcl-2
Antineoplastic Combined Chemotherapy Protocols
Treatment Outcome
Drug Administration Schedule
Multivariate Analysis
Risk Factors
Age Factors
Gene Rearrangement
Patient Selection
Time Factors
Aged
Aged, 80 and over
Middle Aged
Female
Male
Proto-Oncogene Proteins c-bcl-6
Lymphoma, Large B-Cell, Diffuse
Kaplan-Meier Estimate
Antibodies, Monoclonal, Murine-Derived
Biomarkers, Tumor
Rituximab
Precision Medicine
United Kingdom
Research team
Medicine (RMH Smith Cunningham)
Language
eng
License start date
2017-07
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2017, 28 (7), pp. 1540 - 1546