R-CHOP vs R-mini-CEOP in Elderly Patients with Diffuse Large B Cell Lymphoma: An Interim Report from Intergruppo Italiano Linfomi (IIL).

Objectives: CHOP plus Rituximab (R-CHOP) is considered the standard treatment for elderly patients affected from Diffuse Large B Cell Lymphoma (DLCL). The primary objective is to compare in an intent to treat analysis the Event Free Survival (EFS) between R-CHOP and a regimen especially devised for elderly (R-mini-CEOP). Secondary objectives are:

1. to verify the feasibility of a multidimensional score for excluding the frail patients from the study

2. to demonstrate that Rituximab could improve the result of a regimen different from CHOP.

Patients and methods: Patients were previously submitted to 4 multi-item scales: Activities of Daily Living scale (ADL), Instrumental Activities of Daily Living Scale (IADL), comorbidity scale and geriatric scale. The patients who got over were randomised between R-CHOP (day 1:Rituximab 375/m²; Cyclophosphamide 750 mg/m²; Doxorubicin 50 mg/m²; Vincristine 1,4 mg/m²; days 1–4: Prednisone 60 mg/m²) and R-mini-CEOP (day 1: Rituximab 375 mg/m²; Cyclophosphamide 750 mg/m²; Epidoxorubicin 50 mg/m²; Vinblastine 5 mg/m²; days 1–4: Prednisone 60 mg/m²). Both regimens recycled at 21 days and scheduled G-CSF in the days 2–7. An intermediate restaging was scheduled after the first 3 courses.

Results: From March 2003 until July 2005 19 patients were classified “frail”, while 133 patients coming fom 21 Hematology/Oncology Departments were enrolled into the trial. Most of these patients had a severe clinical presentation. Median age was 73 years old. LDH upper than normal value was found in 56% of this group of patients. 72% were in stage III-IV. 25% presented a bulky disease at diagnosis. The two different treatment group were well balanced for number and clinical charatheristics. 72 patients (37 treated with R-CHOP and 35 with R-mini-CEOP) completed the chemotherapy and were assessed for the response. CR rate was 82%. PR rate was 13 %. Five percent progressed during treatment or had no response to the chemotherapy. The overall survival estimated at 13 months was 81 % versus 34 % in frail group (p=0.0001). Despite the use of G-CSF the more frequent side effect was a leucopenia of grade 3–4, which occurred in the 37% of the patients. Severe infections (grade 3–4) occurred in 7% of the patients and in one case was lethal. Toxic deaths were 2%.

Conclusions: The results in terms of CR and feasibility are encouraging. Events which suggest to stop the randomisation have not occurred. The multidimensional score system seems a good tool to identify the patients who are able to tolerate a full dose regimen.