Evaluation of the Effectiveness and Safety of Pixantrone for the Treatment of Multiply Relapsed or Refractory Aggressive Non Hodgkin B-Cell Lymphoma (aNHL) an Observational Multicentre Retrospective Study in a Real World Population
Authors: Navarro Belén , Sancho Juan Manuel , Grasso Cicala Silvina , Spione Mario , Soler Begoña , Zinzani Pier Luigi 
Published: October 2019

Abstract
BACKGROUND: The objective of this study was to evaluate the effectiveness and safety of pixantrone as a rescue treatment for NHL patients in a real world population in Spain and Italy as data on the use of this drug in everyday clinical practice is still scarce.
METHODS: The study included patients aged ≥18 years with histologically proven relapsed or refractory B-cell aNHL who were treated according to pixantrone's product information. Primary endpoint was progression-free survival (PFS). Secondary endpoints included the proportion of patients with complete response (CR), partial response (PR), overall response rate (ORR), overall survival (OS), as well as safety.
RESULTS: 79 patients were included in 52 centers. At diagnosis, mean age was 65 years (95% CI 62-68) and 83% had ECOG 0-1. At pixantrone treatment initiation, 82% of patients presented Ann Arbor stage III-IV, and 64% an International Prognostic Index (IPI) Score ≥3; 85% were refractory and 15% relapsed. Median number of previous therapies was 3 (range 1-5). Patients received a median of two cycles of pixantrone (range 1-6). ORR was 29% with 13.2% CR and 15.8% PR. Median PFS and OS were 2.8 months (95% CI 2.1-3.6) and 4 months (95% CI 3.6-4.4), respectively. There was a trend towards better PFS in relapsed vs refractory patients (12.5 vs 2.6 months, respectively, p=0.059). Patients who received two or more cycles of pixantrone had 38% ORR (CR 17.5%; PR 19.3%). Adverse reactions to pixantrone were reported in 63% of patients. The most frequent toxicities were hematological (67.1%) and gastrointestinal (12%). No febrile neutropenia or clinical cardiotoxicity was reported.
CONCLUSIONS: Although a high percentage of patients with very poor prognostic factors was included in this study (82% Ann Harbor III-IV, 63% IPI ≥3, and 85% refractory), treatment with pixantrone appears to be effective. There was a trend to better efficacy in terms of PFS in relapsed vs refractory patients. In those patients who received ≥2 cycles, pixantrone was more effective compared to those who received less than two cycles, with ORR similar to the pivotal study. Pixantrone treatment resulted active and well tolerated in real world clinical practice.
Keywords: Refractory non-Hodgkin lymphoma; Relapsed non-Hodgkin lymphoma; Salvage therapy; pixantrone.

Disclosures
Sancho: Roche: Speakers Bureau; Janssen: Speakers Bureau; Kern Pharma: Speakers Bureau; Roche: Honoraria; Gilead: Honoraria; Celgene: Speakers Bureau; Mundipharma: Speakers Bureau; Sanofi: Speakers Bureau; Servier: Speakers Bureau; Bristol-Myers: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees. Grasso Cicala:Servier: Employment. Spione:Servier: Employment. Zinzani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau.