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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| Affiliation: | 1. Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey;;2. Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK;;3. Olivia-Newton John Cancer Research & Wellness Centre, Melbourne, Australia;;4. Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge;;5. HMDS, St James’s Institute of Oncology, Leeds;;6. East Kent Hospitals, Canterbury;;7. Department of Hematology, University College London, London;;8. Mount Vernon Cancer Centre, Northwood;;9. Department of Medical Oncology, University of Manchester and the Christie NHS Foundation Trust, Manchester;;10. Department of Hematology, Nottingham City Hospital, Nottingham;;11. Western General Hospital, Edinburgh;;12. Department of Hematology, Torbay Hospital, Torquay;;13. Royal Cornwall Hospital, Truro;;14. Cancer Research UK Center, University of Southampton, Southampton, UK;;15. Institute of Pathology, Würzburg University, Würzburg;;16. Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart;;17. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tübingen, Stuttgart;;18. Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig;;19. Department of Medicine, Saarland University Medical School, Homburg/Saar, Germany |
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| Abstract: | BackgroundThere 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 methodsSix 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.ResultsElderly 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.ConclusionsOur 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 numbersISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60). |
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