Pixantrone Dimaleate (PIX) and Comparators In the Treatment of Relapsed Aggressive Non-Hodgkin Lymphoma (aNHL): An Analysis of Response and Survival by Gender and Age

Abstract

AbstractAbstract 4883 Introduction:Survival after treatment for aNHL is higher in women than men (Leuk Lymph 48:736-745, 2007) and may be worse in elderly patients. We conducted an exploratory demographic subgroup analysis of a phase 3 study that compared PIX, a novel aza-anthracenedione, to single agents in the treatment of patients with multiply relapsed aNHL. Overall, PIX was efficacious on the basis of primary and secondary endpoints. The results from these exploratory analyses suggest that PIX potentially is most efficacious in women and elderly patients even though there are no significant gender- or age-dependent differences in PIX pharmacokinetics. Patients and Methods:This phase 3, randomized, multicenter, controlled, open-label study enrolled patients who had ≥1 prior anthracycline-containing regimen and failed 2 prior treatment regimens for relapsed aNHL (de novo or transformed). Patients (N=140) were randomized to either PIX 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle, for up to 6 cycles, or to investigator's choice of a single-agent comparator (COMP): vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or, in the US only, gemcitabine or rituximab. The primary endpoint was the complete response/complete response unconfirmed (CR/CRu) rate in the intent-to-treat population. Other efficacy endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Response was assessed by an independent radiologic panel. Results:A total of 140 patients were randomized (n=70 per group). The results of the analysis of efficacy by gender and age are shown in the table below. There were no important demographic differences between the study groups or between patients in these exploratory analyses. The differences in CR/CRu rate and ORR between the study groups appeared greater in women than in men and also in patients ≥65 years than in younger patients. PFS and OS were significantly better for women in the PIX group than in the COMP group. During the treatment period, neutropenia and leukopenia were the most common (≥10%) grade 3/4 adverse events and were similar by gender and age. Conclusions:In this phase 3 study, an exploratory subgroup analysis suggests that treatment with PIX appears to provide particular benefit in women and elderly patients and was not accompanied by a meaningful increase in toxicities. These results are limited by small sample sizes and would need to be validated with an additional prospective study. [Display omitted] Disclosures:Singer: Cell Therapeutics, Inc: Employment, Membership on an entity's Board of Directors or advisory committees; DiaKine Therapeutics, Inc: Membership on an entity's Board of Directors or advisory committees. Cernohous: Cell Therapeutics, Inc: Employment. Jurida: Cell Therapeutics, Inc: Employment. Wang: Cell Therapeutics, Inc: Employment. Kuepfer: Cell Therapeutics, Inc: Consultancy, Equity Ownership. Pettengell: Cell Therapeutics, Inc: Honoraria.