Multicenter non-inferiority phase 3 trial of early PET response-adapted treatment in low-risk diffuse large B-cell lymphoma

The multicenter non-inferiority phase 3 LNH2009-1B trial in France evaluated early PET response-adapted treatment in low-risk (age-adjusted IPI risk 0) previously untreated diffuse large B-cell lymphoma (DLBCL) in patients aged 18-80 years. In the experimental arm, patients with negative PET after 2 cycles of R-CHOP received a total of 4 cycles of R-CHOP, whereas those with positive PET after 2 cycles received a total of 6 cycles. In the standard arm, treatment was 6 cycles regardless of PET result after 2 cycles. No radiotherapy was planned. The primary endpoint was 3-years progression-free survival rate. In the PET-adapted arm, 77.7% of patients were PET-negative after 2 cycles, and received in total 4 cycles. The 3-year PFS rate was 92.0% (95% CI 88.3-94.4) in the PET-adapted arm and 89.2% (85.3-92.2) in the standard arm (p=0.070). The non-inferiority of the experimental PET-adapted arm was demonstrated (HR 0.72; p<0.001). Patients in the PET-adapted arm had fewer grade ≥ 3 adverse events (54.7% versus 62.7%; p=0.046) and serious adverse events (9.5% versus 14.2%; p=0.039). The authors conclude that a risk-adapted approach using early PET after 2 cycles of R-CHOP was beneficial minimizing toxicity without compromising efficacy in patients receiving frontline R-CHOP for low-risk DLBCL.