Pixantrone, etoposide, bendamustine, rituximab (P[R]EBEN) as an effective salvage regimen for relapsed/refractory aggressive non-Hodgkin lymphoma-Polish Lymphoma Research Group real-life analysis

Background: Despite a significant improvement in treatment outcomes, 30-40% of aggressive non-Hodgkin lymphomas (NHL) patients are refractory or relapse after the first line therapy. Half of them are not eligible to autologous stem cell transplantation (ASCT) due to failure of platinum-based salvage regimens. Pixantrone is conditionally approved in Europe in patients with R/R aggressive NHL failing at least 2 previous lines of therapy. Polish Lymphoma Research Group (PLRG) evaluated the efficacy and tolerability of P[R]EBEN combining pixantrone, etoposide, bendamustine with or without rituximab), a new regimen developed recently by Francesco d'Amore, in real-life experience.

Methods: In this retrospective audit, we analyzed the data of consecutive 25 R/R NHL cases, treated with P[R]EBEN regimen in 9 PLRG centers. Safety and efficacy data, including adverse reactions (AE), response rates, progression-free and overall survival (PFS and OS) were collected.

Results: Overall response rate (ORR) to P[R]EBEN regimen was 68% (40% CR and 28% PR). Most patients responded, relatively early, by second cycle of therapy. P[R]EBEN was effective in 8 out of 15 patients (53%) refractory to previous platinum-based salvage regimens. In 4 patients (16%) stabilization of disease (SD) during therapy was observed and further 4 patients (16%) progressed during the treatment (PD). Response rates were higher in patients, chemosensitive to their prior regimen (ORR - 87.5%, including 50% CR). At the median follow-up of 7.5 months (range 1-16) the median PFS and OS were not reached. Projected PFS and OS at 12 months are 68% and 78% respectively. The P[R]EBEN regimen was well tolerated and most of patients received it as out-patients. AEs grade ≥3 occurred in 17 patients (68%). Most common grade 3-4 AEs were due to hematological toxicity with febrile neutropenia observed in 5 patients (20%). There were no episodes of septic deaths. Six patients (24%) died during treatment and follow-up period, all of them due to lymphoma progression.

Conclusion: Our data suggest good efficiency and tolerability of P[R]EBEN regimen as a rescue therapy in patients with R/R aggressive NHL.