Preliminary results of a phase II study of rituximab (R), gemcitabine (Gem), oxaliplatin (Ox) plus enzastaurin (ENZ) followed by ENZ maintenance as salvage regimen for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

8069 Background: PKC overexpression is observed in relapsed/refractory DLBCL. Enzastaurin (ENZ), an oral serine/threonine kinase inhibitor, targets PKCβ, and showed preclinical and clinical activity vs. DLBCL. Additionof ENZ may further improve salvage regimen such as R-GemOx in DLBCL pts not eligible for high-dose therapy (HDT). Methods: In this multicenter open-label, single-arm study patients (pts) with relapsed/refractory DLBCL who were not eligible for HDT and transplantation, received up to 8 cycles (cy) of R-GemOx plus ENZ followed by ENZ maintenance for max. 3 years. R-GemOx was administered in 2-weekly cy, with R 375 mg/m2 on day 1, Gem 1,000 mg/m2 and Ox 100 mg/m2 on day 2, plus ENZ 500 mg once daily, with an 1,125-mg loading dose on day 1 of cy 1. Only patients responding after 4 cy continued study treatment to receive 4 additional cy. Primary objective was 1-year progression free survival (PFS). Response rate and safety were secondary objectives. Results: A total of 68 pts with median age 69 years were enrolled between 2/2006 and 10/2008. 85% had received prior rituximab, 71% had only one prior line of chemotherapy, IPI score at relapse 0-2 vs 3-5 was 40% vs 60%. 65% of pts had an early relapse (≤ 12 months). 59% of pts completed more than 4 treatment cycles and 34% completed 8 cycles of therapy and continued with ENZ maintenance. Preliminary results after 4 cycles were: CR/CRu 13 (19%), PR 26 (38%), resulting in an ORR of 57% (CI 45-69%). Grade 3-4 neutropenia and thrombocytopenia were reported for 52% and 43% of the pts. At a max 10% of pts had a grade 3-4 infection during R-GemOx phase. Most common non-hematologic toxicity was neuropathy (4% gr 3). Toxicity during ENZ maintenance was mild: neutropenia 9%, anemia 4%. There were 3 deaths during R-GemOx phase that were possibly related to study drug (septic shock, CVA, ARDS). Conclusions: Given the patient characteristics,preliminary results of R-GemOx plus ENZ followed by ENZ maintenance treatment show an ORR in line with historical data (El Gnaoui, Ann Oncol 2007). Analysis of 1-year PFS rate is ongoing and will be reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Lilly