Related Experiment Video
Updated: Jul 9, 2026
Enhancing Tumor Content through Tumor Macrodissection
Published on: February 12, 2022
Network meta-analysis of first-line R-CHOP-based regimens in MYC/BCL2 double-expressor diffuse large B-cell lymphoma
Hao Cheng1, Lin Zeng1,2, Xuanzhang Li1
1Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
Abstract:
Double-expressor lymphoma (DEL), characterized by concurrent overexpression of MYC and BCL2 without gene rearrangements, represents 20%-30% of DLBCL and confers inferior outcomes with standard R-CHOP. However, no head-to-head trials comparing novel R-CHOP-based regimens specifically in DEL exist. We conducted a frequentist network meta-analysis to compare four modified R-CHOP regimens in treatment-naïve DEL patients. PubMed, EMBASE, Cochrane Library, and Web of Science were searched through December 2025. The efficacy analysis included four studies (CAVALLI, DEB, POLARIX, Randomised Evaluation of Molecular guided therapy for Diffuse Large B-cell lymphoma with Bortezomib (REMoDL-B); 1,016 DEL patients) evaluating Pola-R-CHP, Ven-R-CHOP, VR-CHOP, and CR-CHOP versus R-CHOP in a star-shaped network in which all interexperimental comparisons are purely indirect through the common R-CHOP comparator. For progression-free survival (PFS), Pola-R-CHP was the only regimen achieving statistical significance (HR = 0.65, 95% CI = 0.45-0.94; SUCRA = 76.1%), reducing progression risk by 35%. A supplementary Bayesian analysis confirmed this finding (posterior probability of HR < 1: 90.2%). No regimen significantly improved overall survival (OS). CR-CHOP showed the most favorable OS trend (HR = 0.77, 95% CI = 0.53-1.13; SUCRA = 69.8%). Safety analysis from intention-to-treat populations revealed that Ven-R-CHOP significantly increased grade 3-4 thrombocytopenia (OR = 17.24), neutropenia (OR = 3.42), and anemia (OR = 3.29), whereas Pola-R-CHP demonstrated a safety profile comparable to R-CHOP (any grade 3-4 AE: OR = 1.04). Sensitivity analyses excluding CAVALLI (historical control design), using alternative DEL definitions for REMoDL-B, and excluding REMoDL-B confirmed robustness. Pola-R-CHP may offer a favorable benefit-risk profile in DEL; however, this is based on indirect, subgroup-level evidence of moderate-to-low certainty, and prospective DEL-specific trials are needed for confirmation. The study protocol was registered on INPLASY (registration number: INPLASY202630036; DOI: 10.37766/inplasy2026.3.0036).
Insights
Pola-R-CHP demonstrated improved progression-free survival in double-expressor lymphoma (DEL) patients compared to standard R-CHOP. While no regimen significantly improved overall survival, Pola-R-CHP showed a favorable benefit-risk profile, warranting further investigation in DEL-specific trials.
Area of Science:
- Hematology
- Oncology
- Clinical Trials
Background:
- Double-expressor lymphoma (DEL) is a subtype of diffuse large B-cell lymphoma (DLBCL) characterized by MYC and BCL2 overexpression without gene rearrangements.
- DEL patients typically exhibit poorer outcomes with standard R-CHOP treatment.
- Existing research lacks direct head-to-head comparisons of novel R-CHOP-based regimens specifically for DEL.
Purpose of the Study:
- To compare the efficacy and safety of four modified R-CHOP regimens against standard R-CHOP in treatment-naïve DEL patients.
- To identify the optimal R-CHOP-based regimen for improving progression-free survival (PFS) and overall survival (OS) in DEL.
- To assess the benefit-risk profile of novel regimens in the context of DEL treatment.
Main Methods:
- A frequentist network meta-analysis was conducted, searching PubMed, EMBASE, Cochrane Library, and Web of Science through December 2025.
- Four studies (CAVALLI, DEB, POLARIX, REMoDL-B) involving 1,016 DEL patients were included, comparing Pola-R-CHP, Ven-R-CHOP, VR-CHOP, and CR-CHOP against R-CHOP.
- Efficacy (PFS, OS) and safety (adverse events) were analyzed using indirect comparisons within a star-shaped network, supplemented by Bayesian analysis and sensitivity analyses.
Main Results:
- Pola-R-CHP was the only regimen significantly improving PFS (HR=0.65, 95% CI=0.45-0.94), reducing progression risk by 35%.
- No regimen demonstrated a significant improvement in OS, though CR-CHOP showed a favorable trend (HR=0.77, 95% CI=0.53-1.13).
- Ven-R-CHOP was associated with significantly increased grade 3-4 thrombocytopenia, neutropenia, and anemia, while Pola-R-CHP had a comparable safety profile to R-CHOP.
Conclusions:
- Pola-R-CHP may offer a favorable benefit-risk profile for treating double-expressor lymphoma (DEL) patients, primarily due to improved PFS.
- Current evidence is based on indirect subgroup analyses with moderate-to-low certainty, necessitating caution.
- Prospective, DEL-specific clinical trials are essential to confirm the efficacy and safety of Pola-R-CHP and other novel regimens in this patient population.