Zanbrutinib, lenalidomide plus R‐CHOP (ZR2‐CHOP) as the first‐line treatment for non‐GCB diffuse large B‐cell lymphoma: An updated analysis of efficacy and tolerability

Aims: To evaluate the safety and efficacy of zanubrutinib, lenalidomide plus R-CHOP (ZR2-CHOP) as the first-line treatment for non-GCB DLBCL patients, we updated the results in our cohort. Methods: We enrolled patients aged 18–75 with high-risk non-GCB DLBCL (including double expression and other molecular characteristics). Oral zanubrutinib was given continuously (160 mg twice daily) from Day 0, lenalidomide 25 mg daily Day 1–7. Patients were administered intravenously rituximab (375 mg/m2 Day 0), cyclophosphamide (750 mg/m2 Day 1), doxorubicin (50 mg/m2 Day 1), vincristine (1.4 mg/m2 Day 1), and oral prednisone (100 mg Day 1–5). All patients were recommended to receive 6 cycles of ZR2-CHOP (R-CHOP or R2-CHOP were allowed in cycle 1 due to poor physical condition or inaccessible molecular characteristics at treatment) and patients older than 70 years old were administered ZR2-miniCHOP. Prophylaxis was mandatory with G-CSF in all patients and entecavir in patients with seropositive occult HBV (HBsAg negative but HBcAb positive). CT or PET-CT scans were applied to mid-term efficacy and PET-CT scan was conducted after 6 cycles. ctDNA was dynamically detected baseline, after 3 and 6 cycles to evaluate tumor mutational burden. The primary endpoint was complete response ratio (CRR) at mid-term and after 6 cycles. The secondary endpoint was overall response rate (ORR), ctDNA dynamics and adverse events (AE). AEs were graded based on CTCAE (version 5.0). Results: 30 treatment-naïve non-GCB DLBCL patients were enrolled in this cohort between July 2020 and October 2023. The median age was 55.5. 19 patients (63%) were diagnosed as double-expression (Table 1). At data cutoff (March 2023), the median follow-up was 17 (6–32) months with 27 patients have completed 6 cycles. The ORR was 97% (29/30), with 22 patients achieved CR and 7 patients achieved PR after 3 cycles; 26 (96%) patients achieved CR after 6 cycles (Figure 1). 4 patients have received autologous stem cell transplantation for consolidation after 6 cycles. Molecular subtypes were determined in 18 patients as shown in Figure 2. ctDNA was dynamically detected in 18 patients. 15 (83%) patients achieved undetectable ctDNA after 3 cycles. The 2-year PFS was 79% and the 2-year OS was 100% (Figure 3). The characteristics of 5 patients with progressive disease were listed in table 2. Among them, 3 were of the MCD subtype, 2 had TP53 deletion, 1 had p53 overexpression (80%). Grade 3–4 neutrophil count decreased, thrombocytopenia and anemia occurred in 40%, 30% and 20% of patients, respectively. 6 patients had grade 3 pneumonia and received intravenous antibiotics. Conclusion: ZR2-CHOP for high-risk non-GCB DLBCL patients with fair physical condition could achieve high CRR and early-stage undetectable ctDNA. The overall tolerability was under control. Ongoing Trial Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies No conflicts of interests pertinent to the abstract.