by ecancer reporter Janet Fricker

Brentuximab vedotin - an innovative antibody-drug conjugate -demonstrated encouraging activity in heavily pre treated patients with relapsed or refractory Hodgkin lymphoma (HL), reports a pivotal phase 2 single arm study presented at the American Society of Haematology (ASH) annual meeting and Exposition held December 4-7, 2010 in Orlando, Florida.

"Based on these data, brentuximab vedotin has the potential to change the treatment paradigm for relapsed or refractory HL patients, and could be the first treatment approved for these patients in more than 20 years, said study presenter Robert Chen, from the City of Hope National Medical Center, (Duante, CA, US).

While 70 to 80 % of newly diagnosed patients with adult HL achieve cure with combination chemotherapy consisting of three or four agents together, up to 30 % of patients experience relapse. "These patients have limited treatment options beyond autologous stem cell transplantation and represent a significant unmet medical need," explained Chen, adding that there is currently no FDA approved treatment if disease returns following autologous stem cell transplantation. "The median survival of patients in this study, who had a median age of 31 years, would have been 2.4 years without the new treatment."

Brentuximab vedotin (SGN-35) is an advanced generation antibody-drug conjugate comprising an anti-CD30 antibody attached to monomethyl auristatin E (MMAE). The agent has been designed to be stable in the bloodstream but to release MMAE upon internalization into CD30 expressing tumour cells. Once inside the cell, binding of MMAE to tubulin disrupts the microtubule network, thereby inducing cell cycle arrest, which ultimately results in apoptotic death.

In the current phase 2 single-arm study, 102 patients with relapsed or refractory HL from 26 study centres, (who had previously undergone an autologous stem cell transplant) received brentuximab vedotin 1.8 mg/kg every three weeks as a 30 minute outpatient IV infusion for up to 16 cycles of treatment.

Results show that 75% of patients achieved an objective response (assessed by an independent central review using Cheson 2007 criteria), and furthermore that 34 % of patients achieved a complete response, and 40% a partial response. Among patients achieving a complete remission, the median duration of response had not yet been reached at a median follow-up of approximately one year. Additionally, 94% of patients (96 out of 102) achieved tumour reduction.

"This is very active for a single agent, particularly bearing in mind that patients in this study had failed a median number of 3.5 prior regimens," said Chen adding that response rates for drugs are typically highest when given upfront and usually drop in the second and third line setting.

The most common adverse events were of any grade were peripheral sensory neuropathy (47%), fatigue (46%), nausea (42%), upper respiratory tract infection (37%) and diarrhoea (36%). The most common Grade 3 or 4 adverse events were neutropenia (20%), peripheral sensory neuropathy (8%), thrombocytopenia (8%) and anaemia (6%).

Two additional studies are currently ongoing, added Chen, exploring the use of brentuximab vedotin in the first line setting of HL and immediately post transplant.

Reference

R Chen, A K Gopal, S E Smith. Results of a Pivotal Phase 2 Study of Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma. Abstract 283, ASH Symposium 2010.