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.

Diffuse large B-cell lymphoma: R-CHOP failure—what to do?

“…33 Another study using 131 I-tositumomab-BEAM in comparison with rituximab-BEAM did not reveal any differences between the 2 arms. 34 In a phase 2 study with 131 I-tositumomab given as consolidation after R-CHOP, the CR rate and PFS were not better than with R-CHOP alone in this patient subset. 35 In another phase 2 study with 90 Y-ibritumomab tiuxetan consolidation after R-CHOP, a longer PFS was observed than is usually described (5-year PFS, 78%).…”

Efficacy and safety of pixantrone for the treatment of multiply relapsed or refractory aggressive non‐Hodgkin B‐cell lymphomas

“…10 The first real-world data on pixantrone were published in 2016; a UK-based retrospective study has suggested that patients who relapse >12 months after first-line treatment, those with fewer prior lines of therapy, and relapsed (non-refractory) DLBCL gain greater benefit from pixantrone compared with patients who relapse earlier, have had more lines of prior therapy, or have refractory DLBCL. 11 Despite this evidence, data on the use of pixantrone in everyday clinical practice remain scarce.…”

A retrospective multicentre study of COCKLE, an oral chemotherapy regimen, as palliative treatment for high grade lymphoma

“…The PIX301 trial found a modest progression‐free survival (PFS) advantage with pixantrone monotherapy compared to investigators’ choice of alternative monotherapy, but only recruited 140 patients from 66 centres, of a population which does not represent most patients with relapsed lymphoma. A UK‐wide retrospective study of pixantrone, with a ‘real‐world’ population of older and more frail patients, found worse responses and shorter survival (Eyre et al , 2016b). Furthermore, a press release from the PIX306 trial in July 2018 reported no benefit to R‐pixantrone over R‐gemcitabine (A. Craig, unpublished observations).…”