The efficacy and safety of ZR2 versus R-CHOP-like for elderly patients with newly diagnosed diffuse large B cell lymphoma: a single-center prospective study in China.

Bruton's tyrosine kinase inhibitors have been demonstrated preliminary efficacy in diffuse large B-cell lymphoma (DLBCL). To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients were treated with 6 cycles of ZR2 or R-CHOP-like regimen for the first-line treatment. The primary endpoint was complete response ratio (CRR). The secondary outcome measures were progression-free survival (PFS), overall survival (OS), and adverse events. Between June 15, 2020, and March 11, 2023, 30 patients with ZR2 and 60 patients with R-CHOP-like were enrolled. There were no significant differences observed in CRR (P = 0.878), PFS (P = 0.555) and OS (P = 0.769) between ZR2 and R-CHOP-like group. While, patients in ZR2 group had the following features: significantly older (P = 0.002), more unfit (P < 0.001) and higher prognosis risk scores (P = 0.025). The incidence of grade ≥ 3 anemia (P = 0.008) and pneumonia (P = 0.001) was significantly lower in ZR2 group. Patients with germinal center B-cell-like subtype (GCB), large masses or TP53 mutations had a satisfactory remission rate in ZR2 group (57.1%, 77.8% and 60.0%, respectively). ZR2 and R-CHOP-like regimen had similar efficacy and survival. While, the safety profile for ZR2 was superior. GCB subtype, large masses and TP53 mutations may benefit from ZR2 regimen as well. Patients with EBV-positive and CARD11 mutations may need additional treatment rather than ZR2. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.