Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma: post‐hoc analyses from a phase <scp>III</scp> trial

Pettengell, Ruth; Sebban, Catherine; Zinzani, Pier Luigi; Derigs, Hans Günter; Кравченко, С К; Singer, Jack W.; Theocharous, Panteli; Wang, Lixia; Pavlyuk, Mariya; Makhloufi, Kahina

doi:10.1111/bjh.14101

Cited by 26 publications

(41 citation statements)

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“…9 Subsequent post hoc analyses of this study confirmed that pixantrone was more effective than comparator agents in patients with relapsed or refractory aggressive B-cell NHL in third-or fourth-line settings, independently of previous rituximab therapy. 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.…”

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

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et al. 2020

European J of Haematology

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Eur J Haematol. 2020;104:499-508. | 499 wileyonlinelibrary.com/journal/ejh 1 | INTRODUC TI ON Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL); between 30% and 58% of patients with NHL have DLBCL, which has a crude incidence in Europe of 3.81 cases per 100 000. 1,2 The incidence of both NHL and DLBCL varies considerably between European countries, with Italy and Spain having an incidence of NHL higher than the European average. 1-3 First-line therapy for intermediate-or high-risk B-cell NHL is an anthracycline-based regimen in combination with rituximab, such asAbstract Background and objective: Few treatment options exist for patients with relapsed/ refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who fail first-and second-line therapies. Pixantrone is a novel aza-anthracenedione agent with reduced potential for cardiotoxicity but maintained anti-tumour activity relative to anthracyclines. The current retrospective, observational, real-life study was undertaken in 79 patients who received pixantrone monotherapy for multiply R/R aggressive B-cell NHL in Spain and Italy.Results: Before pixantrone, patients had received a median of 3 prior therapies and 84.6% of them were refractory to the last regimen. Median progression-free survival (mPFS) was 2.8 months (95% confidence interval [CI] 2.1-3.6) and median overall survival (mOS) was 4.0 months (95%CI 5.6-7.9), with an objective response rate (ORR) of 29% (complete remission [CR]: 13.2%, partial remission [PR]: 15.2%). Patients receiving ≥2 cycles of pixantrone showed mPFS and mOS of 3.1 and 6.0 months, respectively, and an ORR of 36.8% (CR: 17.5%, PR: 19.3%). Overall, 63.3% of patients reported ≥1 adverse event (AE), most commonly haematological AEs. One patient developed grade 2 sinus tachycardia. Conclusion:Pixantrone was effective and well tolerated in a real-world population of multiply R/R patients with aggressive B-cell NHL, many of whom had very poor prognostic factors. K E Y W O R D Saggressive B-cell lymphoma, pixantrone, relapse, survival

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

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Campos

et al. 2020

European J of Haematology

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“…Pixantrone monotherapy is approved in Europe in patients with multiply relapsed/refractory aggressive NHL (European Medicines Agency, ). In its pivotal phase 3 trial (PIX301), pixantrone was associated with significantly higher complete response (CR; 20·0% vs. 5·7%) and longer progression‐free survival (PFS; median 5·3 vs. 2·6 months) than comparator in multiply relapsed/refractory aggressive NHL (Pettengell et al , ; Pettengell et al , ). However, at the time when the PIX301 study was conducted, rituximab had not yet become standard treatment for NHL and only 54% of included patients received it before study entry (Pettengell et al , ).…”

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Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B‐cell non‐Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306)

et al. 2019

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PIX306 was a phase 3, randomised, single-blind, multicentre trial conducted in adult patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade 3 who relapsed after ≥1 rituximab-containing regimen and were not eligible for a stem cell transplant. Patients were randomised 1:1 to pixantrone 50 mg/m 2 or gemcitabine 1000 mg/m 2 on days 1, 8 and 15 of a 28-day cycle, combined with rituximab 375 mg/m 2 on day 1, for up to six cycles. Patients were followed for up to 96 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR) and safety. Overall, 312 patients were randomised (median age 73Á0 years). The study did not meet its primary endpoint. Median PFS [95% confidence interval (CI)] was 7Á3 months (5Á2-8Á4) with pixantrone + rituximab (PIX + R) and 6Á3 months (4Á4-8Á1) with gemcitabine + rituximab [GEM + R; hazard ratio (HR): 0Á85; 95% CI 0Á64-1Á14; P = 0Á28]. Median OS was 13Á3 (10Á1-19Á8) months with PIX + R and 19Á6 (12Á4-31Á9) months with GEM + R (HR: 1Á13; 95% CI 0Á83-1Á53). ORR was 61Á9% and 43Á9% respectively and CR rate 35Á5% and 21Á7%. The incidence of adverse events, including cardiac events, was not statistically significant different between PIX + R and GEM + R.

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“…To address these concerns, post hoc subgroup analyses of the phase III trial were conducted, which confirmed the superior efficacy of pixantrone as a salvage therapy. Among 97 patients with aggressive B-cell lymphoma (DLBCL, transformed indolent lymphoma and follicular lymphoma, grade 3 confirmed by blinded centralized review) who were receiving study drug as their third or fourth line of therapy had an ORR of 43.6% versus 12.8% (p = 0.005) and a CR/CRu of 23.1% vs. 5.1% (p = 0.047) for pixantrone versus the comparator agent group [37]. Within this subgroup, analysis of those who had previously received rituximab indicated that treatment with pixantrone was associated with a better response than comparator drug (ORR 45% vs. 11.1%; p = 0.033) [37].…”

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Pixantrone: novel mode of action and clinical readouts

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Cattan

et al. 2018

Expert Review of Hematology

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Pixantrone is a first-in-class aza-anthracenedione approved as monotherapy for treatment of relapsed or refractory aggressive diffuse B-cell non-Hodgkin's lymphoma (NHL), a patient group which is notoriously difficult to treat. It has a unique chemical structure and pharmacologic properties distinguishing it from anthracyclines and anthracenediones. Areas covered: The chemical structure and mode of action of pixantrone versus doxorubicin and mitoxantrone; preclinical evidence for pixantrone's therapeutic effect and cardiac tolerability; efficacy and safety of pixantrone in clinical trials; ongoing and completed trials of pixantrone alone or as combination therapy; and the risk of cardiotoxicity of pixantrone versus doxorubicin and mitoxantrone. Expert commentary: Currently, pixantrone is the only approved therapy for multiply relapsed or refractory NHL, an area with few available effective treatment options. Pixantrone is currently being investigated as combination therapy with other drugs including several targeted therapies, with the ultimate goal of improved survival in heavily pretreated patients. In order for pixantrone to be acknowledged in the treatment of aggressive NHL, the perception of pixantrone as an anthracycline-like agent that has anthracycline-like activity and cardiotoxicity needs to be changed. Further data from ongoing clinical trials will help in confirming pixantrone as an effective and safe option.

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Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma: post‐hoc analyses from a phase III trial

Cited by 26 publications

References 19 publications

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

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

Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B‐cell non‐Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306)

Pixantrone: novel mode of action and clinical readouts

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