Multicenter randomized phase 2 trial of addition of targeted agents to first-line CHOP for peripheral T-cell lymphoma

The multicenter randomized phase 2 GUIDANCE-03 trial in China evaluated addition of targeted therapy to first-line CHOP for peripheral T-cell lymphoma (PTCL). Patients were randomized to 6 cycles of CHOP plus targeted therapy starting in the second cycle (CHOPX; decitabine if TP53-mut, azacytidine if TET2/KMT2D-mut, tucidinostat if CREBBP/EP300-mut, and lenalidomide without these mutations) or CHOP alone. Primary endpoint was complete response rate (CRR) after 6 cycles. The study met its primary endpoint, with CRR 64.6% with CHOPX versus 33.3% with CHOP (OR 0.27; p=0.004). The median follow-up was 24.3 months (IQR 12.0-26.7). The median progression-free survival was 25.5 months with CHOPX versus 9.0 months with CHOP (HR 0.57; p=0.041) while the median overall survival was not reached with CHOPX versus 30.9 months with CHOP (HR 0.55; p=0.088). The most common grade 3 or 4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (65%) and infection (10%), respectively. The authors conclude that targeted agents combined with CHOP were effective and safe first-line treatments for PTCL.