A Matched Comparison of Pola-R-CHP Vs. R-CHOP for DLBCL with Extranodal Involvement

Introduction

Extranodal involvement is a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). Radiotherapy on extranodal lesions or small-molecule drugs such as BTK inhibitors were investigated to increase efficacy. A recent subgroup analysis of the POLARIX study showed that the rate of extranodal involvement was as high as 70% (616/879) in patients with IPI ≥ 2, and Pola-R-CHP had a better survival advantage than R-CHOP in DLBCL with extranodal involvement^[1]. Polatuzumab has been approved for the first-line treatment of DLBCL in combination with R-CHP since April 2023 in China. This real-world retrospective study aimed to compare the efficacy of Pola-R-CHP versus the historical control R-CHOP regimen in the first-line treatment for DLBCL with extranodal involvement.

Methods

We retrospectively analyzed DLBCL patients with extranodal organ involvement who were diagnosed and treated with Pola-R-CHP as first line treatment for at least one cycle in Peking University People's Hospital since April 2024. A matched comparison of Pola-R-CHP versus R-CHOP by IPI score and extranodal organ involvement was conducted with DLBCL database in our institute from January 2015 to January 2023. No radiotherapy was commanded. Efficacy was assessed by PET/CT examination after 3 cycles (interim) and 6 R-chemo+ 2R cycles (end of treatment). Response rates were compared with the chi-square test. Progression-free survival and survival were preliminarily explored using the Kaplan-Meier curve.

Results

41 patients with DLBCL with extranodal involvement were treated with Pola-R-CHP regimen, 21 were GCB type. The median age was 66 (27-86) years, 25 were male, IPI was 4 (2-5), and the median number of extranodal involvement was 2 (1-5). 38 patients completed 3 cycles of treatment and were evaluated, 21 completed induction therapy and were evaluated for efficacy. The median follow-up was 7 months. 88 patients were treated with R-CHOP regimen, 21 were GCB type and 17 were unclassifiable. The median age was 61 (18-83) years, 48 were male, IPI was 4 (2-5), and the median number of extranodal involvement was 2 (1-4). The median follow-up was 44 months.

After three cycles of treatment, the ORR was 35/41 (92%), CR was 28/41 (74%), and PD was 3/41 (8%) in Pola-R-CHP group, which were not significantly different from ORR 77/88 (88%), CR 62/88 (71%), and PD 11/88 (12%) in R-CHOP group. At the end of treatment, in Pola-R-CHP group ORR was 18/21 (86%), CR 17/21 (81%), and PD 3/21 (14%). In R-CHOP group ORR was 70/88 (80%), CR 69/88 (78%), and PD 18/88 (20%). In patients with >1 extranodal involvement, ORR was 22/24 (93%) and CR was 18/24 (79%) at the interim assessment, and ORR was 11/13 (85%) and CR was11/13 (85%) at the end of treatment in Pola-R-CHP group. In R-CHOP group, ORR was 33/40 (83%) and CR was 27/40 (68%) at the interim assessment, and ORR was 29/40 (74%) and CR was 28/40 (70%) at the end of treatment. No significant differences were observed.

The 12-month PFS was estimated to be 92% in the Pola-R-CHP group and 87% in the R-CHOP group (P=0.311).

Conclusion:

Majority of non-low-risk (IPI≥2) DLBCL patients have extranodal involvement. DLBCL with extranodal involvement responds quickly to Pola-R-CHP, especially those with >1 extranodal involvement. Long term survival benefit of Pola-R-CHP in DLBCL with extranodal involvement is expected.

References：

1. Jennifer K. Lue et al. Genomic profiling in a subgroup analysis of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and extranodal (EN) sites of involvement in the Phase III Pola-R-CHP vs R-CHOP (POLARIX) study. 2024 ASCO# 7061.

No relevant conflicts of interest to declare.