Preben: Pixantrone, Rituximab, Etoposide and Bendamustine, Spanish Experience in Diffuse Large B-Cell Lymphoma Treatment

Introduction

Diffuse large B-cell Lymphoma (DLBCL) is the most common subtype of Non-Hodgkin`s Lymphoma. It represents 30% of lymphomas in elderly age, with a 5-year survival of 26-73% depending on the risk factors.

First-line therapies achieve complete response (CR) in 44-87% of cases. Relapsed or refractory (R/R) DLBCL patients to first-line treatment, usually receive salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (SCT) as consolidative therapy.

This second-line therapy is not standardized and normally consists of polychemotherapy combinations. In patients who need third-line therapy, survival results are even worse and nowadays there`s not a protocolized treatment.

Pixantrone offers an alternative for R/R DLBCL patients with efficacy and a favorable safety profile based on a phase 3 clinical trial, which permitted its approval by the European Medicines Evaluation Agency (EMEA). In this study, pixantrone was given as a single-agent salvage therapy in pretreated patients that did not respond to at least two previous chemotherapy regimens, either relapsed or refractory. Patients achieved good responses with low toxicity. Thirty percent of patients achieved objetive responses and 20% CR and not confirmed CRs.

There have been some polychemotherapy combinations with Pixantrone previously described , which obtained better global and CR rates.

Methods

We analyzed R/R DLBCL patients treated with PREBEN scheme in Spain . Treatment regimen was administered as described in d'Amore et al in 13-ICML, 2015: Pixantrone 50 mg/m2 iv day 1 and 8, Rituximab iv or sc day 1, Etoposide 100mg/m2 iv day 1 and Bendamustine 90 mg/m2 iv day 1, given in 3-week cycles, with a maximum number of 6 cycles. We included in the analysis only those patients that had received at least 2 complete cycles.

Results

Five patients were included in the analysis. Median age was 65 years (range, 53-73). Mean number of previous polychemotherapy lines was 3. Autologous SCT addicional had been performed in 3 of them.

Early responses were observed: 3 out of 5 (60%) patients achieved objective responses after cycle 2. One patient remained with stable disease after 4 cycles and one progressed.

Two patients achieved CR, and they were both candidates to receive allogenic SCT after cycle 6.

All of them were treated in the outpatient clinic. They did not need to stay hospitalized to receive this chemotherapy regimen.

Toxicity was less than expected. All patients required complementary treatment with granulocyte stimulating factors but only one patient had febrile neutropenia. Two patients required red blood cells transfusion before starting PREBEN. No patient required platelet transfusions. No unexpected adverse effect or treatment-related deaths were observed .

Conclusions

In our series,R/R DLBCL patients treated with PREBEN achieved 60% of global responses, which are higher than with other schemes in polytreated patients. Toxicity was limited and no unexpected adverse effects were observed.

Altogether, these results provide evidence that PREBEN therapy is effective and safe and encourage us to use it in elderly and young R/R DLBCL patients as a bridge-to-transplantation.

Due to all this, we consider PREBEN safe and effective.