CHMP Recommends Brentuximab Vedotin Plus ECADD for Newly Diagnosed Stage IIB/III/IV Hodgkin Lymphoma

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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of brentuximab vedotin (Adcetris) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (ECADD) for the treatment of adult patients with newly diagnosed, stage IIB with risk factors, III, or IV Hodgkin lymphoma.1

The recommendation was supported by data from the phase 3 HD21 trial (NCT02661503), which showed that brentuximab vedotin plus ECADD reduced the risk of disease progression or death by 34% compared with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP; HR, 0.66; 95% CI, 0.45-0.97; P = .035).2 Patients treated with brentuximab vedotin plus ECADD (n = 738) experienced an estimated 4-year progression-free survival (PFS) rate of 94.3% (95% CI 92.6%-96.1%) vs 90.9% (95% CI, 88.7%-93.1%) for those given eBEACOPP (n = 732).

The estimated 4-year overall survival (OS) rates were 98.6% (95% CI, 97.7%-99.5%) vs 98.2% (95% CI, 97.2%-99.3%), respectively.

HD21 Background

The randomized, multicenter, parallel, open-label trial enrolled adult patients no older than 60 years of age with advanced-stage, classical Hodgkin lymphoma. Patients needed to have Ann Arbor stage III/IV disease, or stage II disease with B symptoms and risk factors of large mediastinal mass and/or extranodal lesions. An ECOG performance status of 0 to 2 and HIV negativity were also required.

Patients were randomly assigned to receive brentuximab vedotin plus ECADD or eBEACOPP. In the experimental arm, patients received brentuximab vedotin at 1.8 mg/kg up to a maximum of 180 mg on day 0, etoposide at 150 mg/m2 on days 1 to 3, cyclophosphamide at 1250 mg/m2 on day 1, doxorubicin at 40 mg/m2 on day 1, dacarbazine at 250 mg/m2 on days 2 to 3, and dexamethasone at 40 mg on days 1 to 4. Treatment cycles lasted 21 days.

PFS and tolerability served as the trial’s primary end points. Secondary end points included complete response rate, OS, gonadal toxicity and function, incidence of second primary malignancies, event-free survival (EFS), and patient-reported outcomes.

Additional data from HD21 showed that among patients with Ann Arbor stage III and IV disease, the 4-year PFS rates were 93.9% (95% CI, 91.9%-95.9%) in the brentuximab vedotin plus ECADD arm vs 91.0% (95% CI, 88.7%-93.4%) in the eBEACOPP arm.

Patients treated in the brentuximab vedotin arm achieved a 4-year EFS rate of 91.4% (95% CI, 89.3%-93.5%) compared with 88.2% (95% CI, 85.9%-90.7%) for those in the BEACOPP arm.

Regarding safety, the rate of treatment-related morbidity was 42% for the experimental arm vs 59% for the control arm (relative risk, 0.72; 95% CI, 0.65-0.80; P < .0001).

The most common any-grade adverse effects included anemia (experimental arm, 98%; control arm, 96%), thrombocytopenia (93%; 86%), leukopenia (98%; 93%), neutropenic fever (21%; 28%), infection (46%; 49%), cardiac disorders (18%; 21%), gastrointestinal disorders (45%; 54%), hepatobiliary disorders (20%; 23%), peripheral sensory neuropathy (49%; 39%), peripheral motor neuropathy (4%, 4%), nervous system disorder beyond neuropathy (28%; 26%), renal and urinary disorders (12%; 10%), respiratory, thoracic, and mediastinal disorders (47%; 38%), skin and subcutaneous tissue disorders (43%; 39%), drug fever (8%; 6%), allergy (5%; 4%), and avascular necrosis (1%; 0%).

Grade 4 anemia, thrombocytopenia, or infection was reported in 52% of patients in the brentuximab vedotin group vs 31% of patients in the eBEACOPP group. The rates of grade 3/4 organ toxicity were 17% and 19%, respectively.

Following the CHMP’s positive opinion, the European Commission will review the marketing authorization application for the brentuximab vedotin–based combination.1

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://www.takedaoncology.com/news/news-releases/positive-chmp-opinion-for-adcetris/
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 Nov 30;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