The investigational monoclonal antibody conjugate brentuximab vedotin (formerly called SGN-35) achieved dramatic responses in patients with relapsed or refractory Hodgkin lymphoma (HL) who had few if any other treatment options. The investigators, as well as other experts, were excited by these findings of a phase II single-arm study presented at the 52nd Annual Meeting of the American Society of Hematology (ASH),¹ which was held December 4-7 in Orlando, Florida. Based on these study results, Seattle Genetics and Millennium (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited) plan to seek regulatory approval in early 2011 for both HL and anaplastic large cell ­lymphoma.

Three-quarters of the 102 high-risk patients with refractory or relapsed HL enrolled at 26 study centers achieved an objective response (greater than 50% of tumor shrinkage), and 34% achieved complete remission. Overall, 94% of patients had some degree of tumor reduction, according to lead investigator ­Robert Chen, MD, Assistant Professor, Hematology and Hematopoietic Cell Transplantation at the City of Hope, Duarte, California.

"Despite responding to front-line combination chemotherapy, up to 30% of all Hodgkin lymphoma patients will relapse. These patients have limited treatment options beyond autologous stem cell transplantation and represent a significant unmet medical need," Dr. Chen told listeners. "Based on these data, brentuximab vedotin has the potential to change the treatment paradigm for relapsed or refractory Hodgkin lymphoma patients, and could be the first treatment approved for these patients in more than 20 years."

Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody and monomethyl auristatin E (MMAE), a potent antitubulin agent. The technology delivers MMAE directly into CD30-expressing cells, prompting apoptosis, and appears to spare non-CD30 cells from toxicity.

Study Details

The single-arm study enrolled 102 patients with relapsed/refractory HL with a median age of 31 years (range, 15-77 years); 53% were female. All patients previously underwent autologous stem cell transplant, and more than 70% had primary refractory disease, failing to achieve complete remission or progressing within 3 months of completing front-line therapy. Also, 39% were refractory to the most recent salvage therapy (excluding autologous transplantation). The median number of prior treatment regimens was 4 (range, 1-13).

Patients were treated with an outpatient infusion of brentuximab vedotin at 1.8 mg/kg every 3 weeks for up to 16 total doses. The primary endpoint was objective response rate as assessed by independent central review.

Median duration of brentuximab vedotin treatment was 29 weeks (range, 3-54 weeks), and the median number of cycles delivered was 9 (range, 1-16). Among patients achieving a complete remission, median duration of response had not yet been reached at the time of the ASH meeting, with a median follow-up of about 1 year.

Toxicity and Response Rates

Side effects (grade 1 or 2) with the investigational drug were manageable and included peripheral sensory neuropathy (47%, most common), fatigue (46%), nausea (42%), upper respiratory tract infection (37%), and diarrhea (36%). The most common grade 3 or higher adverse events included neutropenia (20%), peripheral sensory neuropathy (8%), thrombocytopenia (8%), and anemia (6%).

Dr. Chen acknowledged that peripheral neuropathy was an issue, but said few patients had grade 3 or 4 neuropathy. "Overall, two-thirds of the patients with neuropathy showed improvement or resolution of the side effect during the course of treatment," he commented.

In addition to the impressive 75% objective response rate and 34% complete remission rate, 22% of patients had stable disease, 3% had progressive disease, and 1 patient was not evaluable for response. Progression-free survival among all patients was 25 weeks by independent review and 39 weeks by investigator assessment. At the time of the ASH meeting, progression-free survival had not yet been reached in patients who achieved complete remission.

"Brentuximab vedotin achieves high response rates, has low toxicity, and because of these qualities, outpatient treatment allows patients to continue their daily routine. It has few side effects and most are reversible," Dr. Chen said. ■

Reference

1. Chen R, Gopal AK, Smith SE, et al: Results of a pivotal phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma. 52nd ASH Annual Meeting. Abstract 283. Presented December 6, 2010.