PYRAMID and LYM2034: Targeted randomized phase II studies of bortezomib with or without immunochemotherapy in newly diagnosed nongerminal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL), including rapid prospective non-GCB subtype identification.

TPS226 Background: The recognition of prognostically distinct subtypes of DLBCL by gene expression profiling has, until now, not led to improved outcomes. Conducting targeted studies in prospectively identified, molecularly distinct entities is challenging. PYRAMID and LYM2034 are prospectively identifying and enrolling non-GCB patients (pts). This subtype has inferior outcomes vs GCB following (R-)CHOP alone (Lenz, NEJM 2008; Fu, JCO 2008). The rationale for these studies is provided by data suggesting bortezomib shows benefit specifically in non-GCB DLBCL resulting from inhibition of the critical NF-κB survival pathway, which is activated in the non-GCB subtype. Bortezomib + dose-adjusted EPOCH showed superior response rates and survival in non-GCB vs GCB relapsed DLBCL (Dunleavy, Blood 2009), and in newly diagnosed DLBCL, bortezomib + R-CHOP showed similar outcomes in GCB and non-GCB pts (Ruan, JCO 2010). Methods: PYRAMID is enrolling pts at 55 centers in the US; LYM2034 is enrolling pts at 86 sites in...