ALBERT

Beschreibung: Abstract 2676 Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) has improved the treatment results in DLBCL substantially. With more patients being cured from the lymphoma long term toxicity becomes an even more important issue. By replacing doxorubicin with non-pegylated liposomal encapsulated doxorubicin in the R-CHOP regimen (R-COMP) we tried to reduce the cardiotoxicity of R-CHOP in the 1st line treatment of DLBCL. We randomized 88 patients with untreated DLBCL to one of two treatment arms. R-CHOP consisted of rituximab 375 mg/sqm, cyclophosphamide 750 mg/sqm, doxorubicin 50 mg/sqm, vincristine 2 mg, each iv. day 1 and prednisolone daily po for 5 consecutive days. Six cycles of chemotherapy and 8 cycles of rituximab were planned. In the R-COMP arm doxorubicin was replaced with non-pegylated liposomal encapsulated doxorubicin 50 mg/sqm iv day 1. Forty and 39 patients were eligible in the R-COMP and R-CHOP arm, respectively. The two arms were well balanced with respect to age, smoking status, heart function, hypertension, and international prognostic index. The primary endpoint of the study was the left ventricular ejection fraction (LVEF) measured by the Simpson method at randomization, after each cycle and 8 weeks after the end of treatment. Mean and standard error were compared by the two-sample t test. Mean LVEF was significantly lower in the R-CHOP arm (62.29%) than in the R-COMP arm (63.56%) (P=.0333). Out of all LVEF measurements 10 (4.6%) vs. 31 (15.8%) were

Beschreibung: Abstract 2724 Poster Board II-700 Introduction: Rituximab in combination with chemotherapy achieves the best result in follicular lymphoma. Only limited data are available with rituximab as maintenance in first line setting. Materials and methods: We conducted a prospective multicenter trial in patients with previously untreated follicular lymphoma stage III or IV, which required therapy. Primary endpoint was conversion of BCL2/IgH PCR positivity to negativity. BCL2/IgH was centrally measured by a two-step qualitative PCR in peripheral blood and bone marrow before and after induction therapy, after maintenance treatment and yearly thereafter. Induction therapy (R-FM) consisted of 6 cycles of rituximab 375 mg/qm i.v. day 1, mitoxantrone 10 mg/qm i.v. day 1, fludarabine 25 mg/qm i.v. days 2-4 recyling every 28 days for 6 cycles. I.v. Fludarabine could be substituted by 30 mg/qm p.o. days 2-4 at the discretion of the investigator. Patients not progressing during induction therapy received maintenance rituximab 375 mg/qm every 8 weeks for 12 doses. Results: Twenty-seven patients were entered in the study. Median age was 55 years, (range 32-73 years). Rituximab serum concentrations were measured before and after rituximab infusion during induction and maintenance. Mean rituximab trough serum concentrations before maintenance cylce 1, 2, 4, and 6 were 46, 32, 38, and 37 ng/ml, respectively. Induction R-FM resulted in 16 (59.3%) complete (CR) and 11 (40.7%) partial remissions (PR). During maintenance rituximab 3 patients with PR converted to CR and another 2 progressed. After a median observation period of 33 months 3 year event free and overall survival are 79% (95% CI: .5322; .9168) and 86% (95% CI: .6355; .9544), respectively. In all 19 patients in whom samples were available after the end of R-FM induction BCL2/IgH was negative. During rituximab maintenance therapy 2 of 12 samples became positive for BCL2/IgH. One at relapse on maintenance and the other after completion of maintenance still in clinical CR. Conclusion: With R-FM a high rate of stable remissions can be achieved. Rituximab through serum concentrations were within an effective range. All analyzed BCL2/IgH samples where negative already after induction with R-FM, even though the quality of the remission was improving in some patients during maintenance treatment. The additional effect of rituximab maintenance in first remission remains unclear. The results of randomized trials will elucidate the role of rituximab maintenance treatment in first remission of follicular lymphoma. Disclosures: Fridrik: Bayer: Honoraria, Speakers Bureau; Roche Austria: Honoraria, Research Funding, Speakers Bureau. Off Label Use: Rituximab maintenance in first remission of follicular lymphoma. Greil:Roche: Honoraria, Research Funding. Hopfinger:Roche: Speakers Bureau; Mundipharm: Speakers Bureau. Jaeger:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants.

Beschreibung: Abstract 1766 Introduction: A combination of Rituximab with a chemotherapy regimen consisting of cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP) is the current standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin is known to induce short-time and long-time cardiac toxicity. By encapsulating doxorubicin in liposomes the cardiac toxicity may be reduced. This is the 1st randomised study comparing doxorubicin and liposome encapsulated doxorubicin in the 1st line treatment of DLBCL. Patients and methods: Aim of the study was to reduce the cardiotoxicity of R-CHOP by substituting doxorubicin by liposome encapsulated doxorubicin. The primary endpoint was left ventricular ejection fraction (LVEF) measured by the Simpson method and NT-proBNP levels, respectively. Both parameters were measured before each treatment cycle and after the end of treatment. From December 2007 until July 2010 we performed a two arm prospective randomised study. In arm 1 patients were treated with rituximab 375 mg/m^2 iv day 1, cyclophosphamide 750 mg/m^2 iv day 1, liposome encapsulated doxorubicin (Myocet®) 50 mg/m^2 iv day 1, vincristine 2 mg iv day 1, and prednisolone 100 mg po day 1–5. In arm 2 the regimen was identical, but liposome doxorubicin was substituted by standard doxorubicin 50 mg/m^2 i.v. day 1. Treatment cycles were repeated every 2 to 3 weeks, due to the discretion of the treating physician. Six cycles were scheduled. This study was conducted in accordance with the “Good Clinical Practice” Guidelines and the Declaration of Helsinki and was reviewed by the independent ethics committees at the trial centres. All patients gave their written informed consent. Eighty-eight patients were registered, eight were excluded. In each arm 40 patients were eligible. Median age was 66 years (range 19–84 years), 64% of patients were older than 60 years. The two arms were balanced in respect to age, international prognostic index, smoking status, hypertension, NT-proBNP, and LVEF. At the time of the abstract submission 44 patients (24 and 20 in arm 1 and 2, respectively) had finished their treatment and were fully documented. The complete remission rate was 78.8% and 69.6% in arm 1 and 2, respectively. The two progressive lymphomas were in arm 2. We observed 26 and 32 serious adverse events in 19 and 24 patients in arm 1 and arm 2, respectively. Most of them had neutropenic fever. The mean relative difference in LVEF after the 6th cycle was 2.98 and -3.92 in arm 1 and arm 2, respectively. Two of 24 (8.3%) and 5/20 (25%) had a more than 20% decline of their LVEF during treatment in arm 1 and 2, respectively. However, this was not statistically significant. The difference in median NT-proBNP levels were significantly different 73.1 and 97.2 pg/ml in arm 1 and 2, respectively (P=.0235). Conclusion: In this 1st analyses we did not observe any safety concerns in the two arms. The remission rate was as expected. The substitution of doxorubicin by liposome encapsulated doxorubicin seemed not to alter the efficacy of the treatment. With the limited data available the cardiotoxicity may be lower in the arm with liposome encapsulated doxorubicin. However, the primary endpoint of the study was not met, respective to the attenuation of acute anthracycline cardiac toxicity. A possible attenuation of the frequency and severity of chronic heart failure will need a much longer follow up. The study was registered under the Eudract #: 2007–004970-24 Disclosures: Fridrik: Cephalon: Honoraria, Research Funding. Off Label Use: Liposome encapsulated doxorubicin in diffuse large B-cell lymphoma. Greil:Cephalon: Research Funding.