Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3-5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial.

Abstract

BACKGROUND:

Outcomes for patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy are suboptimal but, to date, no alternative regimen has been shown to improve survival rates. This phase 2 trial aimed to assess the efficacy of a Burkitt-like approach for high-risk DLBCL using the dose-intense R-CODOX-M/R-IVAC regimen.

PATIENTS AND METHODS:

Eligible patients were aged 18-65 years with stage II-IV untreated DLBCL and an International Prognostic Index (IPI) score of 3-5. Patients received alternating cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate) alternating with IVAC chemotherapy (ifosfamide, etoposide and high-dose cytarabine) plus eight doses of rituximab. Response was assessed by computed tomography after completing all four cycles of chemotherapy. The primary end point was 2-year progression-free survival (PFS).

RESULTS:

A total of 111 eligible patients were registered; median age was 50 years, IPI score was 3 (60.4%) or 4/5 (39.6%), 54% had a performance status ≥2 and 9% had central nervous system involvement. A total of 85 patients (76.6%) completed all four cycles of chemotherapy. There were five treatment-related deaths (4.3%), all in patients with performance status of 3 and aged >50 years. Two-year PFS for the whole cohort was 67.9% [90% confidence interval (CI) 59.9-74.6] and 2-year overall survival was 76.0% (90% CI 68.5-82.0). The ability to tolerate and complete treatment was lower in patients with performance status ≥2 who were aged >50 years, where 2-year PFS was 43.5% (90% CI 27.9-58.0).

CONCLUSIONS:

This trial demonstrates that R-CODOX-M/R-IVAC is a feasible and effective regimen for the treatment of younger and/or fit patients with high-risk DLBCL. These encouraging survival rates demonstrate that this regimen warrants further investigation against standard of care.

TRIAL REGISTRATION:

ClinicalTrials.gov (NCT00974792) and EudraCT (2005-003479-19).

• Authors: A K McMillan, E H Phillips, A A Kirkwood, S Barrans, C Burton, S Rule, R Patmore, R Pettengell, K M Ardeshna, A Lawrie, S Montoto, S Paneesha, L Clifton-Hadley, D C Linch
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 31 Issue 9 Pg. 1251-1259 (09 2020) ISSN: 1569-8041 [Electronic] England
• PMID: 32464282 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Ifosfamide
• Prednisone

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Burkitt Lymphoma (drug therapy)
• Cyclophosphamide (therapeutic use)
• Disease-Free Survival
• Doxorubicin (therapeutic use)
• Humans
• Ifosfamide (therapeutic use)
• Lymphoma, Large B-Cell, Diffuse (drug therapy)
• Middle Aged
• Prednisone (therapeutic use)
• Rituximab (therapeutic use)
• United Kingdom
• Vincristine (therapeutic use)
• Young Adult