Up-Front Treatment of Diffuse Large-B Cell Lymphoma (DLBCL) in Elderly Patients with Rituximab in Combination with CHOP-Like Chemotherapy: A Multicenter Study on the Current Clinical Management.
Authors: Canales Miguel A. , de la Serna Javier , Sabin Pilar , Diaz-Mediavilla Joaquin , Provencio Mariano , Ayala Rosa , Perez Ricardo , Alvarez Ana , Sanchez Antonio , Gil Raquel , Hernandez-Navarro Fernando 
Published: October 2019

Abstract
Based on results of GELA study, rituximab in combination with CHOP chemotherapy, given for eight cycles, may be considered the new standard of care for patients older than 60 years diagnosed with DLBCL. However, the afraid of early toxicity and underlying co-morbid illness in elderly patients implies often adjustments in this scheme. The aim of this study was to analyze the routine clinical practice in the up-front treatment of elderly patients (>65 years) with DLBCL. We have enrolled onto this study 80 patients (48 females) with median age 74 years (range, 65 to 85 years) who have been treated with CHOP-like regimens in combination with rituximab as first-line therapy. The 75% of patients had ECOG 0-1, 81% had Ann-Arbor stage III-IV, 41% had B-symptoms, 59% had aIPI 2-3, 39% had bulky disease (> 7 cm) and 55% had elevated beta-2 microglobulin. The most of patients received as up-front therapy R-CHOP (89%); R-CNOP and R-CEOP (doxorubicin is substituted for mitoxantrone and epirubicin, respectively) were the alternative regimens administered. The 57.5% of patients received 6 courses of treatment; the 25% received less than 6 cycles and only the 6% of patients (5 out of 80 patients) received 8 courses of treatment. In 31 out of 80 patients the doses of chemotherapy was reduced; in 20 patients the doses of chemotherapy were reduced in all courses and 2 patients received reduced doses of chemotherapy in 5 out of 6 cycles. In the 40% of patients G-CSF have been administered. The overall response rate was 86% (72% CR/CRu, 14% PR). In the 22 patients who received the lower doses of chemotherapy the overall response rate was 82% (50% CR/CRu) versus 88% in the remaining patients (81% CR/CRu) (p<0.05). Adverse events were observed in the 47.5% of patients and neutropenia was the most frequent complication. In those patients who received reduced doses of chemotherapy less adverse events were observed (13.6% versus 60.3%, p<0.001). With a median follow-up of 15 months, the event-free survival in the assessable population has not been reached (60% at 2 years) and there was no significant difference in those patients who have received the reduced doses of chemotherapy (median 18.5 months versus not reached). The median overall survival has not been reached. At 2 years overall survival is 73% in the entire population and 51% in patients receiving the reduced doses of chemotherapy compared to 80% in the remaining patients but the difference was not statistically significant. In conclusion, in our current clinical practice, 6 courses of chemotherapy (CHOP-like) in combination with rituximab is the commonest regimen used for the treatment of elderly patients. The administration of reduced doses of chemotherapy is associated with both a significant decrease in adverse events and complete response rates and may be translated into a shorter event-free and overall survival. A longer follow-up may be necessary to reveal this difference. Logically, randomized trials are mandatory to address differences between 6 and 8 courses of immunochemotherapy in this population.