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)

Abstract

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.

Current Opinion on Pixantrone in the Treatment of Non-Hodgkin B-Cell Lymphoma

“…10,11 However, the phase III study PIX306, comparing the efficacy and safety of pixantrone with rituximab (PIX-R) versus gemcitabine with rituximab (GEM-R) in patients with relapsed (not refractory) aggressive B-cell NHL, deemed ineligible for ASCT (NTC01321541), failed to demonstrate any improvement in outcomes with pixantrone and rituximab as opposed to gemcitabine with rituximab. [12][13][14] In line with this were also findings of some real-world studies [15][16][17] which have shown overall disappointing outcomes of treatment with pixantrone and have therefore questioned the actual role of pixantrone in the current treatment of R/R aggressive lymphomas.…”

“…No patient subgroups could be identified for whom the PIX-R arm was statistically more beneficial in terms of survival. 14…”

Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies

“…Until recently, the treatment options for the patients who are ineligible for AHCT or those whose lymphoma relapsed after AHCT were limited mainly to chemoimmunotherapy regimens such as R-GemOx (rituximab, gemcitabine, oxaliplatin), BR (bendamustine, rituximab), or pixantrone, or the off-label use of ibrutinib or lenalidomide; all are used with palliative intent given their limited efficacy [8][9][10][11][12][13]. Pixantrone, which was approved by the European Medicines Agency in 2012, also has modest clinical activity in relapsed/refractory DLBCL [14,15]. Historical data of patients with refractory DLBCL treated with the best therapies before the availability of novel treatments showed dismal outcomes with an objective response rate (ORR) and a complete response (CR) rate of 26 and 7%, respectively, and median overall survival (OS) of only 6 months [16].…”

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma

“…The current treatments for DLBCL are mainly dependent on the clinical stages. The limited stage contains stages 1 and 2, the treatment guideline for which suggests the combination of systemic chemoimmunotherapy, including rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and the involved-field radiation therapy[ 3 , 4 ]. However, to some degree, involved-field radiation therapy is not applicable to patients with advanced stages.…”