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

Overview

Journal Ann Oncol

Publisher Elsevier

Specialty Oncology

Date 2020 May 29

PMID 32464282

Citations 21

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

Affiliations

Soon will be listed here.

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).

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