Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma.

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.

Impact of prior treatment on outcome of transformed follicular lymphoma and relapsed de novo diffuse large B cell lymphoma: a retrospective multicentre analysis.

Transformation of follicular lymphoma (FL) into aggressive disease and relapse of de novo diffuse large B cell lymphoma (DLBCL) are considered highly unfavourable events. However, most published data were acquired when rituximab was not routinely used. We retrospectively analysed 50 patients with transformed FL (tFL) in a multicenter study and compared them to 50 individuals with relapsed DLBCL (rDLBCL) who all obtained rituximab for the treatment of their disease. Our goal was to identify factors that predict a more favourable prognosis. After a median follow-up of 5.4 years from diagnosis, there was no significant difference in median overall survival (OS) from the date of transformation (tFL) or date of the first relapse (rDLBCL) (1.9 versus 3.9 years, P = .542). Of note, 5-year OS of patients with tFL was 46 %. Follicular lymphoma patients, treatment naïve prior to transformation, fared significantly better than pretreated patients (median not reached versus 1.4 years, P = .014). Regarding rDLBCL, female gender (13.9 versus 1.8 years, P = .019) and absence of rituximab prior to the first relapse (14.0 versus 1.8 years, P = .035) were favourable prognostic factors in a uni- and multivariate analysis. Only a proportion of patients received high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT), i.e. 38 and 52 % of patients with tFL and rDLBCL, respectively. Our data indicate that a favourable prognosis is conferred by treatment naivety in tFL and by rituximab naivety in rDLBCL. In contrast, we did not find a prognostic impact of HDT-ASCT in our series.

Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network.

PURPOSE: Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. METHODS: Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. RESULTS: This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27% above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1%), as part of third-line to eighth-line therapy for relapse (16.4%), and in refractory disease (12.2%). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3%. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3% in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. CONCLUSION: Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity.

Transformation and additional malignancies are leading risk factors for an adverse course of disease in marginal zone lymphoma.

BACKGROUND: Marginal zone lymphoma (MZL) is a non-Hodgkin lymphoma that occurs as extra nodal, nodal, or splenic. While MZL is generally considered an indolent disease, a substantial percentage of patients follow an unfavorable course. The objective of this retrospective analysis was to identify predictors for a reduced overall survival (OS), or conversely an increased OS. PATIENTS AND METHODS: One hundred and ninety-seven MZL patients were analyzed. Apart from assessing previously published risk factors, concomitant morbidity at diagnosis, transformation into aggressive lymphoma, and occurrence of additional malignancies were evaluated. RESULTS: Next to the known risk factors, i.e. above 60 years of age and elevated serum lactate dehydrogenase (LDH), we demonstrate that transformation into aggressive lymphoma, as well as additional malignancies, are important independent risk factors for a shortened OS in a multivariate analysis, irrespective of the MZL localization. Impressively, in the group of patients lacking LDH elevation, transformation, and/or additional malignancies, only 1 of 63 patients died during follow-up compared with 37 of 87 patients in the high-risk group (HR = 22.8; 95% confidence interval 3.1-167.0; P = 0.002). CONCLUSIONS: Our analysis proposes novel risk factors and warrants for a continuous follow-up to detect the occurrence of transformation and additional malignancies early on.