Effectiveness and Safety of Polatuzumab Vedotin-Based Therapy for Diffuse Large B-Cell Lymphoma: Real-Life Experience from China
Authors: Chen Xi , Yu Haifeng , Li Cong , Xu Jieyu , Lei Tao , Han Shuiyun , Peng Shuailing , Yang Haiyan 
Published: December 2024

Background
Polatuzumab vedotin (Pola) plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) was approved for previously untreated diffuse large B-cell lymphoma (DLBCL) and Pola plus bendamustine and rituximab (Pola-BR) approved for relapsed/refractory (R/R) DLBCL by NMPA in 2023. However, real-world evidence of Pola-based therapy was rare in China. This study aimed to explore treatment patterns, effectiveness, and safety of Pola-based therapy in Chinese patients with DLBCL in real-world setting.
Methods
This retrospective study enrolled either untreated or R/R DLBCL patients who received Pola-based regimen in Zhejiang Cancer hospital from Feb 1, 2023 to May 30, 2024. The primary outcome was complete remission (CR). Progression of survival (PFS), overall survival (OS), and adverse events were analyzed.
Results
This study enrolled 59 patients with DLBCL, with 36 patients in previously untreated DLBCL group (median age 64 [range: 35-81] years, 22[61.1%] females) and 23 patients in R/R DLBCL group (median age 64 [range: 32-81] years, 11[47.8%] females). The number of untreated DLBCL patients with International Prognostic Index (IPI) 0-1, 2, 3, and 4-5 were 4 (11.1%), 4 (11.1%), 11 (30.6%), and 17 (47.2%), respectively. There were 32 (88. 9%) patients with extranodal involvement, 8 (22.2%) with TP53 mutation, and 5 (13.9%) with double-expressor lymphoma (DEL) in previously untreated DLBCL group. In R/R DLBCL group, 20 (87.0%) DLBCL patients were refractory, and 3 (13.0%) patients experienced relapse. The most frequently used regimen were Pola-R-CHP (72.2%) and reduced-dose Pola-R-CHP (Pola-R-mini-CHP) (22.2%) in untreated DLBCL patients, while Pola-BR (52.2%), and Pola plus rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) (26.1%) were most common regimens in R/R DLBCL patients.
During a median follow-up of 205 days (range: 52-552 days), 21 (58.3%) and 12 (52.1%) patients achieved CR in untreated DLBCL group and R/R DLBCL group, respectively. The 6-month PFS rate was 82.9% in untreated DLBCL patients, which was significantly better than 52.7% in R/R DLBCL patients (p=0.046). The 1-year OS rate was numerically higher in untreated DLBCL patients than that in R/R DLBCL patients (88.9% vs. 86.2%, p=0.165). The CR rate was 58.3% in previously untreated DLBCL group, and 3 (75%), 2 (50%), and 16 (57.1%) untreated patients with IPI 0-1, IPI 2, and IPI 3-5 achieved CR, respectively. Untreated DLBCL patients with poor prognostic factor appeared relatively high CR rate, such as 53.1% for extranodal involvement, 37.5% for TP53 mutation, and 40.0% for DEL. Ten patients who completed the prescribed six cycles of treatment reached CR at the end of the treatment period. In R/R DLBCL group, 10 (45.5%) refractory DLBCL patients, and 2 (66.7%) relapsed DLBCL patients achieved CR, respectively. Eight patients received Pola-R-mini-CHP as first-line therapy, and half of them achieved CR. Moreover, 5 untreated patients were ineligible for clinical trial. Four patients with IPI 0-1 were treated with Pola-R-CHP, resulting in 75% CR rate. An 81-year-old patient treated with Pola-R-mini-CHP tolerated the regimen well and achieved CR. Treatment-emergent adverse events (TEAEs) occurred in 46 (80.0%), and 35 (59.3%) DLBCL patients. The proportion of DLBCL patients experienced any grade, and grade 3-4 treatment-related adverse events (TRAEs) were 74.6%, and 55.9%, respectively. No treatment related death or treatment related discontinuation occurred. The most common TEAEs were neutropenia (61.0%), anemia (35.6%), and thrombocytopenia (28.8%).
Conclusions
The application of Pola-based therapy is becoming more prevalent among Chinese patients with DLBCL, including those ineligible for clinical trial. The regimen was modified to be tolerant and beneficial to frail or older patients in clinical practice. Pola-based therapy was effective and safe in Chinese untreated or R/R DLBCL patients with diverse clinical characteristics.