Preliminary Clinical Experience on the Efficacy and Feasibility of a New Combination Regimen Consisting of Pixantrone, Etoposide, and Bendamustine with or without the Addition of Rituximab in Patients with Relapsed/Refractory Aggressive Non-Hodgkin Lymphomas
Authors: d'Amore Francesco , Joergensen Judit , Sillesen Ida Blok , Segel Erik , Bentzen Hans , Thorsgaard Michael , Pulczynski Elisa Jacobsen , Pedersen Bjarne Bach , Gillström Dorte , Clausen Michael , Kamper Peter , Silkjaer Trine , Gormsen Lars C. , Leppä Sirpa , Toldbod Helle 
Published: October 2019

Abstract
Background: With currently available therapies, relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) after high-dose therapy or, in not transplant-eligible patients, after first-line chemotherapy represents an unequivocally unmet clinical need. Aim and Methods: Therefore, we aimed at evaluating a combination chemotherapy regimen based on pixantrone (Pix), a novel aza-anthracenadione recently approved by the European Medicines Agency in adult patients with multiply relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Etoposide and bendamustine were chosen as companion compounds due to available feasibility data in combination with Pix, as well as to their documented efficacy in salvage regimens in relapsed/refractory aggressive NHL and to a well-known feasibility profile when given alone or in combination. The monoclonal anti-CD20 antibody rituximab was added if tumor cells in the relapse biopsy specimen were CD20-positive. The adopted schedule consisted of Pixantrone 50 mg/m2 i.v. day 1+8, Etoposide 100 mg i.v. day 1, Bendamustine 90 mg i.v. day 1 with or without the addition of Rituximab 375 mg/m2 i.v. day 1 (PREBEN/PEBEN). If feasible, each cycle was given at 3-weekly intervals for a maximum of 6 cycles. All patients were assessed for chemosensitivity with PET/CT after cycle 1 or 2. G-CSF support was administered according to local guidelines. Results: A total of 8 evaluable patients with relapsed/refractory aggressive NHL were treated according to the PREBEN/PEBEN schedule. Abstract 5435. Table 1summarizes the clinico-pathological features of the patient cohort along with selected feasibility and efficacy parameters related to the PREBEN/PEBEN regimen (PET/CT status after 1 or 2 courses):Patient characteristicsPREBEN/PEBEN-related parametersPt #DxAgeSexCS at relapseN of prior Rx linesPrior TxN coursesTox grade 3-4Best responseDoR1DLBCL (ABC)70MIV3N6thrombocytopeniaCR*6 mo2DLBCL (ABC)49MIV3Y2-PD-3DLBCL (ABC)53MIV2N2neutropenic fevergoodPR4+ mo4DLBCL (ABC)64MIV2N2neutropenic fevergoodPR3+ mo5DLBCL (GCB)69FIV3N2-CR2+ mo6tFL62MIII3Y2neutropenic feverSD-7tCLL51FIV5Y2neutropenic feverPD-8PTCL-NOS57FIV2N6diarrhoeaCR4+ mo
Baseline (pt#1) after 1 x PREBEN (pt#1)
Figure 1 Figure 1. Figure 2 Figure 2.
Conclusion: The PREBEN/PEBEN schedule is feasible (out-patient regimen) and in individual patients it elicits profound responses early in the course of therapy. A phase 1-2 study in relapsed/refractory DLBCL and PTCL is in preparation.

Disclosures
d'Amore: Amgen: Research Funding; Sanofi Aventis: Research Funding; CTI Life Sciences: Advisory board, Advisory board Other, Speakers Bureau; Mundipharma: Advisory board, Advisory board Other, Speakers Bureau; Takeda: Advisory board, Advisory board Other, Speakers Bureau; Kyowa Kirin Pharmaceuticals: Advisory board Other, Speakers Bureau; Roche: Research Funding.