CHMP Recommends Brentuximab Vedotin/Chemo in Advanced Hodgkin Lymphoma

The CHMP recommended brentuximab vedotin plus ECADD chemotherapy based on positive results from the phase 3 HD21 trial.

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of brentuximab vedotin (Adcetris) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) as a treatment for adult patients with newly diagnosed advanced-stage Hodgkin lymphoma, according to a press release from the developer, Takeda.1

Supporting results came from the phase 3 HD21 trial (NCT02661503) that sought to demonstrate non-inferior efficacy of BrECADD compared with 6 cycles of etoposide, doxorubicin, cyclophosphamide, bleomycin, vincristine, procarbazine, and prednisone (eBEACOPP) in patients with advanced-stage classical Hodgkin lymphoma.2

The trial found that, with a median follow-up of 40 months, the 3-year progression-free survival (PFS) rate was 95.2% (95% CI, 93.7%-96.8%) with BrECADD and 92.3% (95% CI, 90.3%-94.2%) with eBEACOPP; the 4-year PFS rate was 94.3% (95% CI, 92.6%-96.1%) and 90.9% (95% CI, 88.7%-93.1%), respectively (HR, 0.66; 95% CI, 0.45-0.97; P = .035). Across all major subgroups, hazard ratios (HRs) favoring BrECADD were observed.

The 4-year OS rates were 98.6% (95% CI, 97.7%-99.5%) in the BrECADD group and 98.2% (95% CI, 97.2%-99.3%) in the eBEACOPP group, respectively. All 3 treatment-related deaths that occurred were in the BrECADD group; 1 patient in the eBEACOPP group and 3 patients in the BrECADD group had Hodgkin lymphoma as the cause of death.

The event-free survival rate, at 4 years, was 91.4% (95% CI, 89.3%-93.5%) with BrECADD and 88.2% (95% CI, 85.9%-90.7%) with eBEACOPP.

“PET-2-guided BrECADD showed unexpectedly high efficacy with improved tolerability, substantially surpassing that of eBEACOPP,” wrote lead study author Peter Borchmann, assistant medical director in the Department of Hematology and Oncology and head of the Lymphoma Program at the Unvieristy Hosptial of Cologne, Germany, in the paper.2 “With the individualized PET-2-guided, shortened treatment, the BrECADD regimen shows a favorable risk–benefit profile for most patients. Therefore, we recommend BrECADD as a standard treatment option for adult patients with newly diagnosed, advanced-stage, classical Hodgkin lymphoma.”

A total of 1500 patients were randomly assigned, in a 1:1 ratio, to receive either BrECADD (n = 749) or eBEACOPP (n = 751). Eligible patients were 60 years or younger with classical Hodgkin lymphoma of stage III or IV or II with B symptoms and 1 or both risk factors of large mediastinal mass or extranodal lesions. Additional criteria included an ECOG performance status from 0 to 2, freedom from concurrent disease, and HIV negativity.

The trial’s coprimary end points were tolerability defined as investigator-assessed treatment-related morbidity and efficacy assessed by PFS. Secondary end points were adverse events, frequency of complete response, OS, and gonadal toxicity and function, among others.

Additionally, a post hoc analysis of patient-reported outcomes demonstrated that a treatment-related morbidity event was attributed to a lower global health status and lower cognitive, physical, and social functioning at the end of treatment.

At least 1 treatment-related morbidity event occurred in 42% of the BrECADD group and 59% of the eBEACOPP group (relative risk, 0.72; 95% CI, 0.65-0.80; P <.0001); hematologic treatment-related morbidity events occurred in 31% and 52%, respectively (P <.0001). Grade 3 or higher infections were observed in 20% and 19%; grade 3 or higher neutropenic fever occurred in 28% and 21%. Dose reductions occurred most frequently due to thrombocytopenia (23%) in the BrECADD group and leukopenia (34%) in the eBEACOPP group.

Treatment-related morbidity organ toxicity was observed in 19% of the BrECADD group and 17% of the eBEACOPP group (P = .46); sensory peripheral neuropathy was identified in 39% and 49%, respectively.

References

1. Takeda receives positive CHMP opinion for ADCETRIS® (brentuximab vedotin) for the treatment of adult patients with newly diagnosed stage IIb/III/IV Hodgkin lymphoma in combination with ECADD. News release. Takeda. April 25, 2025. Accessed April 25, 2025. https://tinyurl.com/4bvuy4wn
2. Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial [published correction appears in Lancet. 2024;404(10468):2164. doi: 10.1016/S0140-6736(24)02571-6.]. Lancet. 2024;404(10450):341-352. doi:10.1016/S0140-6736(24)01315-1