Safety and effectiveness of brentuximab vedotin in patients with CD30- positive B-cell lymphoma: A multicenter, prospective, observational, real-world BRAVE study in China

Abstract Introduction: Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, has demonstrated effectiveness in CD30-positive lymphomas, particularly relapsed/refractory (R/R) systemic anaplastic large cell lymphoma (sALCL) and R/R classic Hodgkin lymphoma (cHL). Based on the results of the ECHELON-3 study, the U.S. Food and Drug Administration (FDA) has approved the combination of BV with Lenalidomide and Rituximab for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in 2024. The aim of this study is to evaluate the real-world safety and effectiveness of BV in adult patients with CD30-positive B-Cell lymphoma (BCL) patients in clinical setting in China. Methods: The BRAVE study was a multicenter, observational, prospective study conducted across 32 centers in China. Eligible participants included patients aged ≥18 years, with confirmed CD30-positive lymphoma who received BV-containing treatment regimens. The primary endpoint was serious adverse events (SAEs). The secondary endpoints were AEs, dose intensity, objective response rate (ORR), complete response (CR), progressive-free survival (PFS) and overall survival (OS). Results:A total of 84 CD30-positive BCL patients (pts) were enrolled between June 7, 2021, and June 19, 2024. Among 54 newly diagnosed (ND) cases, 14 were primary mediastinal large B-cell lymphoma (PMBCL) and 34 were DLBCL; of 30 R/R cases, 8 were PMBCL and 20 were DLBCL. The median age at baseline was 43.0 years (interquartile range (IQR): 30.5-65.0), 52.4% were male. Patients aged 60 years accounted for 33.3%. ECOG score ≥ 2 was 18.5% and 27.6% for ND and R/R pts, respectively. IPI score ≥ 3 was reported in 51.5% and 33.3% for ND and R/R pts, respectively. 66.7% of both ND and R/R pts were at Ann Arbor stage Ⅲ-Ⅳ. Extranodal involvement was observed in 53.7% of ND and 46.7% of R/R pts. Overall, 20.2% (17 pts) experienced SAEs, with 4 (4.8%) pts experiencing death. Only one hematologic SAE (1.2%) was reported, which was identified as myelosuppression. The most common non-hematological SAEs were infection (7.1%). 71.4% (60 pts) experienced AEs of any-grade, with 27.4% (23 pts) experiencing grade ≥ 3 per CTCAE criteria. Adverse drug reactions (ADRs) were observed in 39.3%, and no ADR-related mortality occurred. In ND pts, the median dose intensity was 1.67 (IQR: 1.39-1.85) mg/kg with a median dose of 4.5 (IQR: 3.0-6.0) cycles, and the majority of pts (58.7%) received the BV-R (Rituximab) -CHP (Cyclophosphamide, Doxorubicin and Prednisone) regimen. Response assessments were performed in 10 ND PMBCL and 23 ND DLBCL, median time to response (TTR) was 2.89 (IQR: 2.20-2.96) and 2.86 (IQR: 2.23-3.65) months in PMBCL and DLBCL, respectively. The ORR was 90% (95% CI, 55.5%-99.7%) in PMBCL and 82.6% (95% CI, 61.2%-95%) in DLBCL, with CR rate of 40% and 56.5%, respectively. At a median follow-up of 12.9 (95% CI, 9.3-14.8) months, the 1-year OS rate was 82.4% (95% CI, 62.4%-92.4%), with 1-year OS rates of 85.7% in PMBCL and 84.7% in DLBCL. For R/R pts, the median dose intensity of 1.72 (IQR: 1.45-1.82) mg/kg with a median dose of 2.0 (IQR: 2.0-4.0) cycles. Response assessments were performed in 7 R/R PMBCL and 16 R/R DLBCL, the median TTR was 1.92 (IQR: 1.68-2.71) months, the ORR was 100% (95% CI, 59.0%-100%) in PMBCL and 50.0% (95% CI, 24.7%-75.3%) in DLBCL, with CR rate of 28.6% and 25.0%, respectively. At a median follow-up of 8.8 (95% CI, 6.2-18.4) months, the 1-year OS rate was 73.2% (95% CI, 49.5%-87.1%). CD30 expression analysis was available in 62 pts, with median expression level of 70% (IQR: 30%-80%), and there was no statistically significant difference in treatment response between pts with median CD30+ expression more or lower than 70%: ORR (80.0% vs 76.2%, p = 0.7893) and CR rate (53.3% vs 52.4%, p = 0.9556), respectively. Conclusions: The real-world BRAVE study demonstrated that BV was well tolerated and showed promising effectiveness in Chinese patients with ND and R/R BCL regardless of the CD30 expression status. These findings suggest the potential of broader clinical applicability of BV in BCL management.