Rituximab and Reduced Dose CHOP (R-mini-CHOP) for Patients Over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study LNH03-7B

Half of the cases of DLBCL occurs in patients over 65 years but very few data are available for patients over 80 years. These older patients however seem to respond as younger patients when treatment can be tolerated. In the aim to evaluate tolerance and efficacy of a reduced dosage chemotherapy regimen associated with rituximab in this population, the GELA initiated in 2005 a prospective, multicenter, phase II study.

Patients older than 80 years with untreated CD20+ DLBCL, Ann Arbor stage I with bulky mass to IV and a performance status (PS) of 0 to 2 were eligible. Patients were treated with mini-CHOP chemotherapy (cyclophosphamide: 400 mg/m² D1; doxorubicine: 25 mg/m² D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m² by oral route from D1 to D5) plus rituximab (375 mg/m² D1) every 21 days for 6 cycles. GCSF was optional. The primary objective was to evaluate the efficacy of R-mini-CHOP as measured by the overall survival. Secondary endpoints were response rate, progression free survival (PFS), event-free survival (EFS), disease-free survival (DFS) for complete responders and toxicities. Survival results are presented on an intend-to-treat basis. Response to treatment was evaluated according to 1999 Cheson criteria.

One-hundred-and-fifty-patients (51 male, 99 female) were included in 38 centers of the GELA. The median age was 84 years (range 80–95). Seventy-five percent of patients had a stage III/IV. LDH level was elevated in 69% of patients. Age-adjusted (aa) IPI was 2–3 in 66% of patients. One-hundred-twenty-nine patients completed the first three cycles and 108 received the whole regimen. The Dose-Intensity for patients who completed the three first cycle was 100% and 96.8% for doxorubicine and cyclophosphamide respectively. Thirty-six percent of patient received at least one injection of GCSF. The overall response rate was 74%, including 40% of complete response and 23% of unconfirmed complete response. At the time of this analysis, in July 2010, the median follow-up time was 20 months. The 2-year overall survival was 58.9% [95% CI: 49.3–67.2%]. The two-year estimated PFS, EFS and DFS were 47.4% [95% CI: 38.1–56.2%], 44.8% [95% CI : 35.7–53.6%] and 56.6% [95% CI : 49.3–67.2%] respectively. Hematological toxicity was the most common side effect. Grade 3–4 neutropenia was observed in 39% of the patients and grade 3–4 thrombocytopenia in 7%. Eleven patients (7%) experienced at least one episode of febrile neutropenia. Overall patients experienced a median of 4 nights of hospitalization during treatment phase (range 0–46).

Thirty patients died during the treatment evenly distributed between treatment toxicity (6.7%) lymphoma (6.7%) and intercurrent causes (6.7%). In a univariate analysis, PS 0 or 1, aaIPI 0 or 1, number of extra-nodal sites <2, albumin level >35g/l, mass <10cm and a high IADL (Instrumental activities of daily living) score appear to be highly predictive of a prolonged survival. In a multivariate analysis a PS equal to 0 or 1 and an albumin level >35 g/l were significantly associated with a longer survival.

In patients over 80 years with DLBCL and a good performance status, immunochemotherapy with R-mini-CHOP appears to be safe and effective, indicating that a substantial proportion of very old patients could indeed be cured. This regimen could be considered as a platform for the introduction of new drugs in the first line treatment of this population.

No relevant conflicts of interest to declare.