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Introduction:Anthracyclines plays a key role in the treatment of Diffuse Large B cell Lymphoma (DLBCL). There is a great concern about its cardiotoxicity, especially among elderly patients with raising age and related morbidities. Liposomal doxorubicin (LD) has proven to be efficacious and less cardiotoxic in combinations of neo-adjuvant chemotherapy regimes through phase II and III studies in breast cancer. There are some phase II studies in DLBCL but to our knowledge, controlled randomized studies are pending.

Alegre: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

INTRODUCTION

Introduction: Indolent B cell non-Hodgkin lymphomas are entities without curative treatment nowadays. However, survival has significantly improved since the incorporation of immunomodulatory agents and now immunochemotherapy has become the gold standard. Most treatment strategies use progression free survival (PFS) as a surrogate marker for overall survival (OS), although updated long term results are frequently lacking. Since 1990 our group introduced IFNα-2b to Bagley’s CVP induction regimen, for naïve indolent NHL (LNH-pro study). Herein we report our long term results.

Patients with Mantle cell lymphoma (MCL) have an adverse outcome after relapse due to chemorefractory disease with conventional treatments. Bendamustine, a nitrogen mustard compound chemically related to the alkylating agents, has demonstrated high efficacy with a low toxicity profile in reported clinical trials.To analyze the Spanish experience in patients with relapsed/refractory MCL treated with Bendamustine.Retrospective analysis of spanish experience in relapsed/refractory MCL treated with Bendamustine alone or in combination. This study has been approved by local ethical committees.Currently, there are 36 patients registered and 28 are available for this analysis. Patients'characteristics: 69% male, median age 65 years old (range 41–81), 87% ECOG≤ 1, 83% Ann Arbor stage IV, 37% high risk MIPI and 9% blastic variant. Previous regimens were CHOP or CHOP like ± R in 42.5%, HyperCVAD/MtxAraC ± R in 42.5%, R-CVP in 9% and other regimens in 6%. Median number of previous treatments were 2.6 (range 1–6), all patients had received prior Rituximab and 73% had chemosensitive disease to the last treatment. Bendamustine regimen was R-B (R-375mg/m2 D1, B-90 mg/m2 D1-2) in 78% patients, R-B with B-70 mg/m2 in 8%, B alone in 3%, R-B-Bortezomib in 3% and R-B plus consolidation (SCT, Y90Ibritumomab-tiuxetan) in 8%. Median number of cycles was 4.61 (range 1–7). G- CSF support was administered in 43% of cycles. Response: Overall response rate was 73%, with 43% CR & uCR and 30% PR. Survival: Median overall survival from diagnosis is 8,26 years (range: 1.6–11,6 years) without plateau. Median progression free survival (PFS) after Bendamustine treatment was 16 months (95% CI: 11.7–20.4), data that compares favourably with patients' PFS to previous therapy (12 months, 95% CI: 6.5–17.5). Median PFS for patients who achieved CR/uCR is 32.6 months (95% CI: 19.9–45.4) versus 11 months in patients with PR (95% CI: 3.9–18.8). With a median follow-up for surviving patients of 12 months since Bendamustine treatment, the estimated OS at 3 years is 47% (+ SD 14%). Toxicity: No treatment related mortality has been described so far. Over 152 cycles, only 10 hospitalizations due to febrile neutropenia were reported. No one case of lysis tumoral syndrome has been reported.Bendamustine plus Rituximab is a good rescue treatment in non selected pretreated patients with mantle cell lymphoma. CR rate and duration of response seem to reproduce in current clinical practice the good data reported in previous clinical trials and compares favourably with other available treatments.No relevant conflicts of interest to declare.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing affected patients a highly variable outcome. The improvement in survival gained with the addition of rituximab to CHOP chemotherapy (R-CHOP) led to re-define the international prognostic index (IPI). The new index, known as revised IPI (R-IPI), showed to be simpler as it groups the patients in only 3 risk groups. However, the effect of prior rituximab-therapy upon the usefulness and significance of previously recognized prognostic factors on patients relapsed or refractory and receiving subsequent treatment with rituximab plus chemotherapy in DLBCL remains unexplored. Biological parameters, including expression of Bcl-6, Bcl-2, p53 and MUM-1 have been described as IPI-independent prognostic factors.The objective of this study was to evaluate the benefit of the R-IPI to predict the outcome of DLBCL patients at the relapse time following a front line treatment with chemotherapy and rituximab. We also aimed to establish in this population the relationship between immunohistochemical expression of biological parameters and outcome.Patients and methods: this was a multicentric, observational, post-authorization and cross-sectional study (ClinicalTrials.gov identifier: NCT01369784). Inclusion criteria were: patients with age ≥ 18 years with DLBCL refractory/relapsed after first line treatment with rituximab, with or without transplantation. Patients must have finished a rescue treatment including rituximab. Written informed consent was obtained from participants. When the data of the biopsies at diagnosis and relapse were available, immunohistochemical results of bcl-2, bcl-6, p53 and MUM-1 were obtained.152 patients were included (146 evaluables) with a median age of 58 years. At LDBCG diagnosis 48% had > 1 extranodal localization (29% had bone marrow disease), and 30% had ECOG 2 or greater. Eighty-one percent presented stages III or IV and 72% had elevated LDH. Three percent had very good prognosis R-IPI, 69% good prognosis R-IPI and 27% poor prognosis R-IPI. Most patients received R-CHOP as first line therapy. Overall response rate was 79% (40% complete remission). Relapse was confirmed with biopsy and histological study in 55 patients. At relapse 31% presented > 1 extranodal localization, 30% ECOG 2–4, 64% stages III-IV and 72% elevated LDH. R-IPI prognostic groups distribution at relapse were as follows: 8% very good, 75% good and 27% poor. R-ESHAP and R-GEMOX were the two more used rescue therapies resulting in 60% overall response rate (31% complete remission). R-IPI at relapse was significantly associated (p < 0,05) with overall response rate following R-chemotherapy rescue therapy. None of the immunohistochemical parameters analized correlated with rescue therapy results.This is the largest reported series analizing R-IPI in DLBCL at relapse/refractory in patients receiving R-chemotherapy. In this series of patients R-IPI calculated at the relapse time was the only prognostic factor capable of predicting the overall response to the second line of treatment. Thus R-IPI prognostic score is a simple and useful predictor for outcome in DLBCL at relapse/refractoryNo relevant conflicts of interest to declare.

Abstract 4942

Abstract 3654This icon denotes a clinically relevant abstract

Survival of Follicular Lymphoma patients has significantly increased with the introduction of immunomodulatory agents, such as Interferon (IFN) and Rituximab (R). Until 2002 our Follicular Lymphoma patients were included in a trial and received induction therapy with CVP + Interferon (LNH-pro, JCO 16; 1538–1546). Since 2006, Rituximab is being added to the same induction regimen (LNH-pro-05, EHA 09). Herein we communicate the comparative results between these two trials in Intermediate-High risk Follicular Lymphoma patients.To compare toxicity and efficacy in terms of complete remission (CR) and Progression Free Survival (PFS) between both trials in Intermediate-High risk Follicular Lymphoma patients.Patients in the LNH-pro trial (1990-2006) received CVP (CY 400mg/m2 p.o D1-5, VCR 1.4mg/m2 iv D1, PRD 100mg/m2 po D1-5) + IFN (3MU/m2 sc, 3 times/wk, for 12 wks). When it became available, G-CSF support was permited. In the LNH-pro-05 trial (2006-ongoing), Rituximab (R: 375mg/m2 iv D1) was added to the same induction regimen. All patients received 8 cycles as per protocol, with G-CSF support and Pn. jiroveci prophilaxis. In both studies, complete re-assessment was performed after cycle 4, at the end of induction therapy, every 4 months for the first 2 years and every 6 months thereafter.We analysed data from 74 and 36 FL patients with FLIPI≥2, included in the LNH-pro and LNH-pro-05 trials, respectively. Patients' characteristics are shown in table 1. No significant differences were found between groups, except for a higher incidence of elevated B2-microglobulin in patients treated with CVP+IFN and higher Bulky disease (>7cm) among patients with R+CVP+IFN. Median number number of cycles were 6 and 8, respectively. Response: Seventy one patients (96%) in the LNH-pro Trial (CVP+IFN) were evaluable for response. Overall Response (OR) rate was 87%, with 68% Complete Remission (CR) and 19% Partial Remission (PR) (9% non-responders).In the LNH-pro-05 Trial (R+CVP+IFN), 36 patients (92%) and 33 patients (83%) were evaluable for response after 4th and 8th cycle. At cycle 4, all assesed patients achieved remission (15% PRs and 85% CR+uCR), while after the 8th cycle 100% of patients are in CR or uCR. Toxicity. Main hematologic grade 3–4 toxicity was neutropenia, 33% for CVP+IFN and 28% for R+CVP+IFN, with 12% and 6% of infections, respectively. Other non-hematologic toxicities were infrequent and mild (5% and 10% in each group). Eight percent of patients in the LNH-pro trial withdrew treatment due to toxicity. At the moment, none of the patients in the LNH-pro-05 trial have experienced an unacceptable toxicity. Survival . Median follow-up was 7.7 years for CVP+IFN and 2 years for R+CVP+IFN. A significant increase of PFS was seen among patients who received R (66% vs. 86%, at 3 years, P 0.05). There is also a trend to a longer overall survival in patients treated with R+CVP+IFN (P 0.07).The addition of Rituximab to CVP+IFN induction regimen in Intermediate-High risk Follicular Lympoma patients, significantly increases complete remission rates (88% to 100%) and progression free survival (86%, at 3 years), with a low toxicity profile.No relevant conflicts of interest to declare.

Abstract 2867