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 1

summarizes 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 parameters
Pt # Dx Age Sex CS at relapse N of prior Rx lines Prior Tx N courses Tox grade 3-4 Best response DoR 
1 DLBCL (ABC) 70 M IV 3 N 6 thrombocytopenia CR* 6 mo 
2 DLBCL (ABC) 49 M IV 3 Y 2 - PD - 
3 DLBCL (ABC) 53 M IV 2 N 2 neutropenic fever goodPR 4+ mo 
4 DLBCL (ABC) 64 M IV 2 N 2 neutropenic fever goodPR 3+ mo 
5 DLBCL (GCB) 69 F IV 3 N 2 - CR 2+ mo 
6 tFL 62 M III 3 Y 2 neutropenic fever SD - 
7 tCLL 51 F IV 5 Y 2 neutropenic fever PD - 
8 PTCL-NOS 57 F IV 2 N 6 diarrhoea CR 4+ mo 
Patient characteristicsPREBEN/PEBEN-related parameters
Pt # Dx Age Sex CS at relapse N of prior Rx lines Prior Tx N courses Tox grade 3-4 Best response DoR 
1 DLBCL (ABC) 70 M IV 3 N 6 thrombocytopenia CR* 6 mo 
2 DLBCL (ABC) 49 M IV 3 Y 2 - PD - 
3 DLBCL (ABC) 53 M IV 2 N 2 neutropenic fever goodPR 4+ mo 
4 DLBCL (ABC) 64 M IV 2 N 2 neutropenic fever goodPR 3+ mo 
5 DLBCL (GCB) 69 F IV 3 N 2 - CR 2+ mo 
6 tFL 62 M III 3 Y 2 neutropenic fever SD - 
7 tCLL 51 F IV 5 Y 2 neutropenic fever PD - 
8 PTCL-NOS 57 F IV 2 N 6 diarrhoea CR 4+ mo 
View Large

Baseline (pt#1) after 1 x PREBEN (pt#1)

Figure 1
Figure 1.
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Figure 2
Figure 2.
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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.

Topics:
bendamustine, etoposide, lymphoma, non-hodgkin, pixantrone, rituximab, diffuse large b-cell lymphoma, febrile neutropenia, chemotherapy regimen, computed tomography/positron emission tomography imaging, lymphoma, t-cell, peripheral

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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