Brentuximab in Classical Hodgkin Lymphoma — In the Clinic

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Brentuximab vedotin is an anti-CD30 monoclonal antibody that targets the Reed-Sternberg cells found in patients with classical HL.
Brentuximab vedotin is an anti-CD30 monoclonal antibody that targets the Reed-Sternberg cells found in patients with classical HL.

Hodgkin lymphoma (HL) is a B-cell driven hematological malignancy with 2 main subgroups — classical and nodular lymphocyte predominant — which are distinguished by cellular morphology and immunophenotype.1 Treatment for classical HL is determined after staging, which is performed using the Ann Arbor staging system with Cotswolds modifications.2 This staging system ranges from stage I (involving a single lymph node region) to stage IV (non-contiguous extralymphatic involvement).3

Classical HL was treated with the same regimen for over 40 years: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).4 Yet close to 30% of patients with stage III or IV HL developed  relapsed or refractory disease after treatment with ABVD, which prompted research into other options. And in addition to the risk of treatment failure, each component of the regimen is associated with toxicities that can be irreversible and increase with each successive dose. Doxorubicin is known most for its cardiac toxicity, bleomycin for pulmonary toxicity, and vincristine for neuropathy. Even if a patient responds well to ABVD, she/he is therefore at risk for serious adverse events during and after treatment.

Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that targets the Reed-Sternberg cells found in patients with classical HL. Until recently, BV was approved only for relapsed or refractory HL, though, based on newly reported data from the ECHELON-1 trial (ClinicalTrials.gov Identifier: NCT01712490), the US Food and Drug Administration (FDA) approved BV as a first-line treatment for patients with stage III or IV disease.

ECHELON-1 was a multicenter, open-label, international phase 3 clinical trial that compared BV+AVD with ABVD as first-line therapy for patients with stage III or IV classical HL. The BV group received 1.2 mg per kg of body weight, which is lower than the traditional use of 1.8 mg/kg used as monotherapy.5 Both groups received the same dosing of AVD. The primary endpoint was modified progression-free survival (mPFS), defined as the time to progression, death, or incomplete response and use of subsequent chemotherapy. Secondary endpoints included overall survival (OS) and complete response rate.

Six hundred and sixty-four patients received BV+AVD and 670 received ABVD. BV+AVD had a significantly higher 2-year mPFS rate of 82.1% compared with 77.2% in the ABVD group. This represented a hazard ratio for mPFS of 0.77 for the BV+AVD group. No secondary endpoints met statistical significance.

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