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
Mené sur 111 patients atteints d’un lymphome diffus à grandes cellules B à haut risque de récidive (âge médian : 50 ans), cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression à 2 ans, d’une stratégie de chimiothérapie de première ligne de type R-CODOX-M/R-IVAC (alternance par cycles d’un traitement combinant cyclophosphamide, vincristine, doxorubicine et hautes doses de méthotrexate, puis d’un traitement combinant ifosfamide, étoposide et hautes doses de cytarabine, tous deux dispensés avec le rituximab)
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 pts 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 and IVAC (cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate [CODOX-M] alternating with ifosfamide, etoposide and high-dose cytarabine [IVAC]) chemotherapy plus 8 doses of rituximab. Response was assessed by CT after completing all 4 cycles of chemotherapy. The primary endpoint was 2-year progression-free survival (PFS). Results : 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. 85 patients (76.6%) completed all 4 cycles of chemotherapy. There were 5 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% 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 PS ?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.