FDA Approval of Brentuximab Vedotin With Chemo Offers New Hope for Stage III/IV Hodgkin Lymphoma

The first U.S. Food and Drug Administration (FDA)-approved regimen in front-line stage III or IV classical Hodgkin lymphoma in more than 40 years is now heading to the clinic. On March 20, 2018, brentuximab vedotin in combination with chemotherapy was granted approval to be used in adult patients with previously untreated stage III or IV classical Hodgkin lymphoma. The approval is based on the successful outcome of the phase III ECHELON-1 clinical trial that compared brentuximab vedotin plus AVD (adriamycin, vinblastine, and dacarbazine) to ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine).

Joseph Connors, MD, the clinical director of the Center for Lymphoid Cancer at BC Cancer in Vancouver, Canada, said the standard of care for patients with stage III or IV classical Hodgkin lymphoma basically has not changed over the last four decades. However, the ECHELON-1 study demonstrated superior efficacy of brentuximab vedotin plus chemotherapy when compared with the standard of care while removing bleomycin. He said this represents a meaningful advance because it means less toxicity for patients as well as the potential for better outcomes.

“ABVD is unsatisfactory in two ways. First, it fails to cure the disease in 25% to 30% of patients and second ABVD can have major, sometimes fatal toxicity. The most dangerous drug in the ABVD combination is bleomycin, which can rarely, unpredictably, cause fatal lung toxicity,” Dr. Connors told Cancer Network. “This represents a very useful step forward in treating this disease.”

The trial included 1,334 patients and it showed that after patients received an average of six 28-day cycles of treatment of brentuximab vedotin plus AVD, they were 23% less likely to experience progression, death, or initiation of new therapy compared with those receiving ABVD. There were 117 (18%) patients in the brentuximab vedotin plus AVD arm who experienced disease progression, death, or began new therapy compared with 146 (22%) patients on the ABVD arm.

Common side effects of brentuximab vedotin include neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia. In the current clinical trial, 67% of patients treated with brentuximab vedotin plus chemotherapy developed peripheral neuropathy and 91% of patients developed neutropenia. Preventative treatment with granulocyte colony-stimulating factor is recommended with brentuximab vedotin plus chemotherapy for the first-line treatment of stage III or IV classical Hodgkin lymphoma.

Brentuximab vedotin is already approved to treat classical Hodgkin lymphoma after relapse, classical Hodgkin lymphoma after stem cell transplant when a patient is at high risk of relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment, and primary cutaneous ALCL after treatment failure.

Brentuximab vedotin is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E. It is now being investigated in more than 70 clinical trials, including two ongoing phase III studies: the ECHELON-2 trial in front-line mature T-cell lymphomas and the CHECKMATE 812 trial in combination with nivolumab for relapsed/refractory Hodgkin lymphoma.