The majority of patients (pts) with diffuse large-B cell lymphoma (DLBCL) are elderly and may have limited tolerance to chemotherapy due to concomitant diseases. Non-pegylated liposomal doxorubicin has an improved therapeutic index in comparison to doxorubicin, resulting in less myelosuppression, lower GI toxicity and reduced risk of cardiotoxicity at dose level equivalent to standard formulations of doxorubicin. The aim of this study was to assess the efficacy and feasibility of the combination of cyclophosphamide, vincristine, prednisone and liposomal doxorubicin with rituximab every three weeks (R-COMP21) in DLBCL elderly pts with concomitant disease or relapsed pts pre-treated with anthracyclines containing regimens. We analysed twenty-five not consecutive pts from June 2003 to December 2005 according to following negative characteristics: 5 pts over 75 years (20%), 8 pts pretreated with anthracyclines (32%), 12 pts (48%) with heart disease (5 ischemic, 2 hypokinetic and 5 hypertensive cardiomiopathy). Median age was 71 years (range 54–76). 3 pts were stage I, 6 stage II, 5 stage III and 11 stage IV. According to IPI score 8 pts were low risk, 9 low-intermediate, 7 intermediate-high and 1 high risk. The median left ventricular ejection fraction (LVEF) at diagnosis was 59% (range 42%–75%). All pts were evaluable for response to therapy: 18 (72%) obtained a complete remission (62,5% in pre-treated pts), 5 (20%) obtained a partial remission with an overall response rate of 92%. Two pts did not respond to therapy. After a total of 126 cycles we observed three toxic event (congestive heart failure, stroke and gastrointestinal bleeding). No significant hematological toxicity was recorded. Four percent of cycles were delayed. Median final LVEF was 57% (47%–65%). All pts but one had no change in LVEF, one patient developed a congestive heart failure resolved with medical therapy: he was withdrawn due to decrease of LVEF. After a median observation period of 2 years (range 2–68 months), 71% of pts are alive, five pts died two due toxicity and three due to progressive disease. We compared these outcomes with an historical control of 26 aggressive NHL pts treated from February 2001 to June 2005; these pts received no doxorubicin (10 pts) or a mitoxantrone-based scheme devised for elderly (16 pts) due to age or concomitant disease. Case matching was performed with respect to clinical stage, IPI, sex, symptoms, bulky disease, LVEF, with the exception of age (which was greater in control group: median 76 vs 71 p=.001) and heart disease which was more frequent in experimental group (48% vs 31% p=.02). Allowing for the limitations of studies using historic controls, the R-COMP regimen was associated with higher CR (72% vs 42%) and OS rates (71% vs 42%). These results did not change when only pts treated with rituximab are considered. We conclude that the general tolerability and the low incidence of cardiac events of liposomal doxorubicin warrants further studies in a subset of pts with concomitant disease limiting the use of conventional anthracyclines.

Disclosures: We used this drug in a phase two study.

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