title: Results of a multicentre UK-wide retrospective study evaluating the efficacy of pixantrone in relapsed, refractory diffuse large B cell lymphoma.
abstract: Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in those unfit or ineligible for autologous stem cell transplantation is associated with a poor outcome and new treatment approaches are needed. Pixantrone is a novel aza-anthracenedione which is structurally similar to anthracyclines and is licenced in R/R DLBCL and National Institute for Health and Care Excellence (NICE)-approved following the PIX301 trial. No data exist post-NICE approval. We performed a UK-wide retrospective multi-centre study of 92 R/R DLBCL who received pixantrone. Eighty-five per cent had refractory disease and 72% had an international prognostic index (IPI) 3-5 at commencement of pixantrone. The median progression-free survival (PFS) was 2·0 months (95% confidence interval (CI) 1·5-2·4) and the median overall survival was 3·4 months (95% CI 2·7-4·5). The overall response rate was 24% (complete response 10%; partial response 14%). We demonstrate that pixantrone has limited activity in a cohort of high risk, predominantly refractory DLBCL. Multivariate Cox regression revealed that patients who relapsed >12 months after first line treatment, those with fewer prior lines of therapy and relapsed (non-refractory) DLBCL had improved PFS. The major population of unmet need are those with refractory DLBCL who are poorly represented within trials and in whom pixantrone appears less efficacious compared to relapsed DLBCL.
authors.affiliation: Department of Haematology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors.forename: Toby A
authors.initials: TA
authors.lastname: Eyre
authors.affiliation: Department of Medical Oncology, the Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Linton
authors.affiliation: Imperial College London Centre for Haematology, Hammersmith Hospital, London, UK.|Department of Haematology, Royal Free Hospital, London, UK.
authors.forename: Phillipa
authors.initials: P
authors.lastname: Rohman
authors.affiliation: Department of Haematology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors.forename: Jaimal
authors.initials: J
authors.lastname: Kothari
authors.affiliation: Department of Haematology, Royal Free Hospital, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Cwynarski
authors.affiliation: Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Kirit
authors.initials: K
authors.lastname: Ardeshna
authors.affiliation: Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Bailey
authors.affiliation: Department of Haematology, Newcastle upon Tyne NHS Foundation Trust, London, UK.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Osborne
authors.affiliation: Department of Haematology, Cardiff and Vale University Health Board, Cardiff, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Rowntree
authors.affiliation: Department of Haematology & Stem Cell Transplantation, Birmingham Heartlands Hospital, Birmingham, UK.
authors.forename: Dewi
authors.initials: D
authors.lastname: Eden
authors.affiliation: Department of Haematology & Stem Cell Transplantation, Birmingham Heartlands Hospital, Birmingham, UK.
authors.forename: Paneesha
authors.initials: P
authors.lastname: Shankara
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Eyre
authors.affiliation: Department of Haematology, Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon, UK.
authors.forename: Parag
authors.initials: P
authors.lastname: Jasani
authors.affiliation: Imperial College London Centre for Haematology, Hammersmith Hospital, London, UK.
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Chaidos
authors.affiliation: Department of Haematology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Collins
authors.affiliation: Department of Haematology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
authors.forename: Chris S
authors.initials: CS
authors.lastname: Hatton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000627:therapeutic use; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D059005:Topoisomerase II Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; C086548:pixantrone
keywords: DLBCL; anthracycline; aza-anthracenedione; pixantrone