Brentuximab Vedotin, Chemotherapy Combination Improves Overall Survival in Newly Diagnosed Advanced Hodgkin Lymphoma

Results from a clinical trial investigating brentuximab vedotin (Adcetris; Seagen) in combination with chemotherapy found that the treatment significantly improved overall survival (OS) in patients with newly diagnosed advanced classical Hodgkin lymphoma, according to a Seagen press release.

Brentuximab vedotin is an antibody-drug conjugate comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE). The antibody-drug conjugate employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.

With approximately 6 years of median follow up, researchers found that patients receiving brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) in the frontline setting had a 41% reduction in the risk of death compared with patients receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The safety profile of brentuximab vedotin was also consistent with previous studies and no new safety signals were observed.

“These groundbreaking results are important for patients with advanced classical Hodgkin lymphoma given that an improvement in overall survival has rarely been shown in frontline treatment of this disease,” said Roger Dansey, MD, chief medical officer at Seagen, in the press release. “We look forward to presentation of the results at an upcoming medical meeting.”

Classical Hodgkin lymphoma is a cancer of the blood that begins when lymphocytes grow out of control. Individuals with classical Hodgkin lymphoma have abnormal white blood cells called Reed-Sternberg cells in their lymph nodes. These cells usually have a special protein on their surface called CD30, which is a key marker of classical Hodgkin lymphoma. CD30 is present in approximately 95% of all cases of Hodgkin lymphoma, according to the press release.

In 2022, the American Cancer Society estimates that there will be about 8540 new cases of Hodgkin lymphoma. Furthermore, an estimated 920 individuals will die of the disease in the United States.

Echelon-1 is an open-label, international, randomized, phase 3 trial evaluating the safety and efficacy of frontline brentuximab vedotin plus AVD versus ABVD in 1334 adults with stage III or IV classical Hodgkin lymphoma. Participants were randomly assigned to receive A+AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. OS is a key secondary endpoint, and the primary endpoint is modified progression-free survival.

In addition to the indication for previously untreated stage III or IV classical Hodgkin lymphoma in combination with AVD, brentuximab vedotin is indicated for the treatment of classical Hodgkin lymphoma at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation; for classical Hodgkin lymphoma after failure of auto-HSCT or failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates; and for previously untreated systemic anaplastic large cell lymphoma (sALCL) for other CD30-expressing peripheral T-cell lymphomas.

Patients can also be treated with brentuximab vedotin if they have sALCL after failure of at least 1 prior multi-agent chemotherapy regimen, or for patients with primary cutaneous anaplastic large cell lymphoma or CD30-expressing mycosis fungoides who have received prior systemic therapy.

REFERENCE

Adcetris Combination Significantly Improves Overall Survival in Newly Diagnosed Patients With Advanced Hodgkin Lymphoma. News release. Seagen; February 3, 2022. Accessed February 3, 2022. https://investor.seagen.com/press-releases/news-details/2022/ADCETRIS-Combination-Significantly-Improves-Overall-Survival-in-Newly-Diagnosed-Patients-with-Advanced-Hodgkin-Lymphoma/default.aspx