R-CHOP vs R-MiniCEOP in Elderly Patients with Diffuse Large B-Cell Lymphoma (B-DLCL) Prospectively Selected by a Multidimensional Evaluation Scale: Preliminary Results of a Randomized Study Performed by Intergruppo Italiano Linfomi (IIL).

In 2003 the IIL started a randomized trial for the initial treatment of elderly patients with B-DLCL with the aim of comparing efficacy of standard R-CHOP chemotherapy vs less intensive R-miniCEOP regimen. The study was also aimed at assessing the usefullness of a Multidimensional Evaluation Scale (MES) for the prospective identification of patients eligible to full doses chemotherapy. Main inclusion criteria were; age ≥ 65 years, histologically confirmed B-DLCL, stage II-IV, non-frail status. Patients’ frailty was assessed before randomization by MES which included: comorbidity, ADL(Activities of Daily Living), IADL (Instrumental ADL) and geriatric syndrome (Dementia, delirium, depression, incontinence, osteoporosis, falls, failure to thrive) scales. Patients were defined frail in case of ≥ 3 grade III or 1 grade IV comorbidities, score <6 at ADL scale, or in case of geriatric syndrome. Eligible patients were centrally randomized in a 1:1 ratio between 6 courses of standard R-CHOP-21 regimen and 6 courses of R-miniCEOP-21 (vinblastine 5mg/sqm instead of vincristine; epidoxorubicin 50mg/sqm instead of doxorubicin). G-CSF use was recommended. Event free survival was chosen as principal study endpoint. From Feb 2003 to Dec 2006, 288 patients were registered in the study: 52 patients were defined frail at MES and were treated at phisician discretion; among non-frail cases 2 patients were excluded (stage I disease;concomitant neoplasia) and 27 cases have not been validated yet by the study trial office for pending data. The clinical characteristics of of the 209 fully validated randomized cases (104 and 105 cases assigned to R-CHOP and R-miniCEOP, respectively) were: median age 72 years (range 65 to 85), male gender 47%, Stage III-IV 69%, > 1 ENS 27%, aaIPI ≥2 47%; clinical features were well balanced between the two regimens. Overall 70% of patients achieved CR without differences between arms (75% and 65% for R-CHOP and R-miniCEOP, respectively; p=0.173); 18 cases were withdrawn from study for early death (14) or treatment toxicity (4). Grade III-IV anemia occurred in 8% of cases (p=NS), grade III-IV neutropenia in 23% of cases (p=NS), grade III-IV infections in 4% (p=NS). After a median follow-up of 16 months for alive patients (range 1 to 52), 2-year EFS and OS were 54% (95% CI: 45% – 61%) and 70% (95%CI: 61%– 77%), with no differences between study arms. Analysis of MES data did not identify any comorbid condition, or ADL, or IADL scores of prognostic relevance. Among 53 patients defined frail by MES, treatment was planned with curative intent (R-CHOP, R-miniCEOP, P-VEBEC) in 28 cases. For these cases a worst outcome was observed compared to non-frail patients (2yr OS of 43% vs 70%; p=0.007). In conclusion MES represents a valid tool for identifying elderly patients with B-DLCL eligible to full doses chemotherapy and its use is recommended for future trials.The addition of Rituximab to a less intensive chemotherapy regimen (mini-CEOP) represent a good alternative to standard R-CHOP for the treatment of elderly patient with B-DLCL.