NEW ORLEANS—Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with International Prognostic Index (IPI) scores of 3-5 at diagnosis have poor prognosis despite improvements seen with addition of rituximab (R) to CHOP therapy (cyclophosphamide, doxorubicin, vincristine, prednisone; R-CHOP).
Enzastaurin inhibits PKCβ, which is a component of the B-cell receptor signaling complex, and results of a phase 2 trial in patients with relapsed DLBCL suggested clinical activity.
But disappointingly, results of the multinational phase 3 randomized, double-blind, placebo-controlled PRELUDE trial, reported at the 55th American Society of Hematology Annual Meeting and Exposition, suggest that post-R-CHOP enzastaurin therapy does not improve patient survival.
“Enzastaurin did not improve DFS (disease-free survival), EFS (event-free survival), or OS (overall survival) in patients with high-risk DLBCL and complete response following R-CHOP treatment,” reported Michael Crump, MD, FRCPC, of Princess Margaret Cancer Center in Toronto, Ontario, Canada, and coauthors.
A total of 758 patients were enrolled between the years of 2006 and 2010 (n = 504 receiving enzastaurin, n = 254 placebo), the authors reported. Median follow-up time was 48 months (range, 0.03-80 months). Enzastaurin-associated adverse events included chromaturia (18.5% vs. 0.4%), QTc prolongation (10.8% vs. 3.6%), and diarrhea (10.3% vs. 2.8%).
“There were no significant differences in number of patients with at least one grade 3 or higher AE between treatment arms,” the coauthors reported. “No significant differences were observed in the frequency of deaths while on therapy.”
Coauthors included employees of Eli Lilly and Company and research funding was provided by Eli Lilly.