R-Vemp Is a Safe and Effective Chemo-Immunotherapeutic Regimen In Elderly Unfit DLBCL Patients: Report From a Single Center-Experience

Background and objectives The standard first-line therapy for patients with DLBCL includes R-CHOP or CHOP-like regimens; although these regimens are highly effective in the majority of DLBCL patients , elderly \u201cunfit\u201d patients do not tolerate these schedules and usually receive palliative therapy with a consequent dismal prognosis. Several polychemotherapy regimens combining low toxicity and a substantial anti-lymphoma activity have been tested in this clinical setting. In the pre-rituximab era, VEMP (etoposide, cyclophosphamide, mitoxantrone, prednisone) polychemotherapy was investigated initially in relapsed/refractory patients and subsequently as first line therapy and displayed fairly good outcomes. In this study, we present data from an Italian single-center experience evaluating the efficacy and tolerability of the association of Rituximab with VEMP (R-VEMP) in patients not eligible for standard R-CHOP therapy or its modifications (for example R-miniCHOP) because of age and/or comorbidities. Design and Methods From October 2006 to November 2012, 34 untreated patients aged 66 years and older (median age: 79) with DLBCL (26% GC, 48% non-GC, 26% ND) were treated with a combination chemotherapy including etoposide 150 mg/m2 day 1; cyclophosphamide 650 mg/m2 day 1; mitoxantrone 12 mg/m2 day 1; prednisone 60 mg/m2 day 1-5; rituximab 375 mg/m2 day 0). Sixty-eight percent of patients had high Charlson Comorbility Index; 62% had Ann Arbor stage III/IV disease; 47% had high or intermediate-high International Prognostic Index score. Results Twenty-six patients (76%) completed the scheduled treatment (4 or 6 cycles). The Overall Response Rate (ORR) was 71%: 19 patients (56%) obtained a Complete Response (CR), 5 (15%) achieved a Partial Response (PR); 3 patients (9%) were in stable disease and 7 (20%) had a progressive disease (among these latter, 6 patients were intermediate-high or high IPI score and had extranodal disease; all of these patients had high Charlson Comorbility Index). After a median follow-up of 20 months, 15 patients (44%) maintained a CR and only one patient relapsed within 14 months after achieving a CR. In this setting of patients the median Overall Survival (OS) was 20 months (range 1-78), the Event Free Survival (EFS) was 6 months (range 1-41). The treatment was well tolerated without therapy related mortality. Among the adverse events, the most common were: grade 3-4 temporary neutropenia (71%), grade 2 transitory anemia (29%) and febrile neutropenia (20%). G-CSF was administrated to 29 patients (85%) and erythropoiesis stimulating agents to 8 patients (24%). Conclusions These data suggest that R-VEMP is a well-tolerated and highly effective regimen in elderly \u201cunfit\u201d patients with DLBCL and could offer a valuable alternative choice for those patients not eligible for more toxic first line protocols. Considering the high rate of serious adverse events and the difficulty to completely administer the scheduled cycles, standard R-CHOP or CHOP-like therapy is applied with much less frequency to elderly unfit patients. R-VEMP could represent a reasonable regimen that warrants to be further explored, as an additional therapeutic option in order to overcome the low survival rate observed in this subgroup of patients

Integrated CLL Scoring System, a New and Simple Index to Predict Time to Treatment and Overall Survival in Patients With Chronic Lymphocytic Leukemia

NTRODUCTION: Several prognostic factors have been identified to predict the outcome of patients with chronic lymphocytic leukemia (CLL), but only a few studies analyzed more markers together. PATIENTS AND METHODS: Taking advantage of a population of 608 patients, we identified the strongest prognostic markers of survival and, subsequently, in a cohort of 212 patients we integrated data of cytogenetic lesions, IGHV mutational status, and CD38 expression in a new and easy scoring system we called the integrated CLL scoring system (ICSS). ICSS defines 3 groups of risk: (1) low risk (patients with 13q(-) or normal fluorescence in-situ hybridization analysis results, mutated IGHV, and CD38) (2) high risk (all 11q(-) or 17p(-) patients and/or all unmutated IGHV and CD38(+) patients); and (3) intermediate risk (all remaining patients). RESULTS: Using only these 3 already available prognostic factors, we were able to properly redefine patients and better predict the clinical course of the disease. CONCLUSION: ICSS could become a useful tool for CLL patients' management