Efficacy and safety of R-CDOP in treatment-Naïve non-Hodgkin lymphoma with high tumor burden: A multicenter, prospective study

Abstract Background: Treatment of non-Hodgkin lymphoma (NHL) with high tumor burden remains challenging, and treatment with R-CHOP in this population require further optimization. Pegylated liposomal doxorubicin (PLD) offers a promising alternative to conventional doxorubicin, leveraging enhanced permeability and retention effects for longer circulation and less cardiotoxicity. Aims: This study evaluated the efficacy and safety of PLD combined with R-COP (R-CDOP) in treatment-naïve (TN) NHL patients with high tumor burden. Methods: In this single-arm, multicenter, prospective trial (NCT05040555). TN patients with CD20+ diffuse large B-cell lymphoma or grade 3b follicular lymphoma with high tumor burden were recruited. Patients are considered to have high tumor burden if they meet at least one of the following criteria: (1) presence of at least three lymph nodes with a diameter of 3 cm or more; (2) presence of any lymph nodes or extranodal masses with a diameter of 7 cm or more; (3) presence of hepatomegaly and splenomegaly confirmed by PET-CT; Spleen: female 15cm, male 16cm); (4) presence of pleural and peritoneal effusions determined through cytological examination, flow cytometry, or diagnosed by PET-CT, (5) LDH levels exceeding 3 times the upper limit of normal value, and (6) PET-CT TMTV exceeding 220cm3. The patients received R-CDOP: Rituximab (375mg/m2, d0), PLD (30-35mg/ m2, d1), Cyclophosphamide (750mg/ m2, d1), Vindesine (3mg/ m2, d1) / Vincristine (1.4mg/m2, d1) and Prednisone (60mg/ m2, d1-5) every 21 days for 4 (Limited-stage lymphoma) or 6 (Advanced lymphoma) cycles with an additional 2 cycles of Rituximab therapy. The primary endpoint was objective response rate (ORR). The secondary endpoints were complete response rate (CRR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: From November 13, 2021 to December 14, 2024, 64 eligible patients were enrolled. The median age was 64.5 (range, 34-77) years, with 63 cases of diffuse large B-cell lymphoma (DLBCL), and 1 case of follicular lymphoma (FL) 3b or DLBCL. Forty-nine patients (76.6%) with stage III-IV. Among 59 efficacy-evaluable patients, the ORR and CRR were 86.4% (51/59) 95%CI, 75.0%-94.0% and 52.5% (31/59) 95%CI, 39.1%-65.7%, respectively. The DCR was 93.2% (55/59) 95%CI, 83.5%-98.1%. The subgroup analysis results indicated that for high-risk, advanced-stage, patients with abnormal LDH levels, and those with dual expression, promising therapeutic effects were observed. At a median follow-up of 11.6 months, the median PFS and the median OS were not reached, with a 1-year PFS rate of 75.8% and a 1 -year OS rate of 81.7%. The most common grade 3/4 treatment-related adverse events (TRAEs) were neutropenia (17.2%), leucopenia (12.5%) and anemia (14.1%). One patient (1.6%) experienced mild atrial premature contractions and no congestive heart failure occurred. Conclusions: The preliminary results of the study demonstrated promising efficacy and a manageable safety profile for the R-CDOP regimen in treatment-naïve NHL patients with high tumor burden, supporting further investigation.