Pivotal Phase 2 Study Involving Brentuximab Vedotin in Hodgkin Lymphoma Patients

Orlando—A pivotal phase 2, single-arm, multicenter study found that brentuximab vedotin was safe and effective in patients with relapsed or refractory Hodgkin lymphoma who had undergone an autologous stem cell transplant (ASCT). Robert Chen, MD, assistant professor of hematology and hematopoietic cell transplantation at the City of Hope National Medical Center, discussed the findings at a press briefing and oral abstract session at the ASH meeting. The session was titled Results of a Pivotal Phase 2 Study of Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma. Unlike other lymphoma types, Hodgkin lymphoma contains a characteristic type of cell known as the Reed-Sternberg cell, which expresses the CD30 antigen. In 2010, Hodgkin lymphoma will be diagnosed in 8500 patients in the United States, according to the American Cancer Society. Each year, there are >30,000 cases of Hodgkin lymphoma worldwide. Studies have shown the majority of patients with Hodgkin lymphoma are cured with combination chemotherapy of 3 or 4 agents, but ≤30% of patients relapse or are refractory to front-line treatment. These patients have few options other than to undergo additional chemotherapy regimens followed by an ASCT. According to Dr. Chen, approximately 50% of patients who undergo ASCT relapse. The US Food and Drug Administration has not approved any treatment options for patients whose disease returns after an ASCT. Brentuximab vedotin, an investigational antibody-drug conjugate, delivers monomethyl auristatin E to Hodgkin lymphoma cells. The drug induces cell death through an anti-CD30 antibody, the researchers said. In this trial, the primary end point was the overall objective response rate; secondary objectives included assessing the duration of response, progression free survival (PFS), and overall survival (OS). The study enrolled 102 patients at 26 centers in the United States, Canada, France, and Italy with a median age of 31 years who had received a median of 3.5 prior chemotherapy regimens. To be included, patients had to be ≥12 years of age, have a measurable disease of ≥1.5 cm, an Eastern Cooperative Oncology Group performance status between 0 and 1, and a prior ASCT. Of the patients, 71% were primary refractory, failing to achieve complete remission (CR) to front-line chemo therapy or relapsing within 3 months. In addition, 42% of patients were refractory to their most recent prior therapy. Patients received 1.8 mg/kg of brentuximab vedotin administered intravenously over a 30-minute period every 21 days. They received a maximum of 16 total doses and had follow-up appointments every 12 weeks. An independent review facility assessed the results and found 75% of patients had achieved an objective response (95% confidence interval [CI], 65%-83%), including 34% CR and 40% partial remission.Patients had a median duration of response of 29 weeks (95% CI, 16-52). The median duration of CR had not been reached, and the estimated 12-month OS was 88%. In addition, 94% of patients achieved tumor reductions, PFS was 25 weeks, and PFS among patients achieving CR and median OS had not been reached, according to the poster presenters.