Adcetris (Brentuximab Vedotin): A New Treatment Strategy for Relapsed or Refractory Hodgkin Lymphoma (HL) and Systemic Anaplastic Large Cell Lymphoma (ALCL)Current Standard of Care Approximately 5 -10% of HL patients are refractory to initial treatment

Approximately 10 -30% of HL patients will relapse after achieving an initial complete remission

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard of care for patients who are initially refractory to therapy or who relapse following a response to treatment

Ansell SM, Armitage JO. Management of Hodgkin lymphoma. Mayo Clin Proc 2006;81:419-26Limitations of Existing StrategiesPatients with relapsed or refractory CD30-positive lymphoproliferative disorders such as Hodgkins lymphoma and anaplastic large-cell lymphoma commonly have a poor prognosis. Patients with these histologies who subsequently progress after salvage chemotherapy and autologous stem cell transplantation have very limited treatment options and are in need of novel effective therapies.

Ansell SM. Expert Opin Investig Drugs. 2011 Jan;20(1):99-105. Epub 2010 Dec 2.Limitations of Existing Strategies Approximately 1300 deaths result from disease progression after ASCT each year in the US

Survival after ASCT failure is approximately 26 months

Treatment-related mortality at 1 year is approximately 20% with 2-year overall survival at only 50% in patients who progressed after ASCT and were treated with reduced intensity ASCT

Kewalramani T, Nimer SD, Zelenetz AD, et al. Progressive disease following autologous transplantation in patients with chemosensitiverelapsed or primary refractory Hodgkins disease or aggressive non-Hodgkins lymphoma. Bone Marrow Transplant 2003;32:673-9

Robinson SP, Goldstone AH, Mackinnon S, et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 2002;100:4310-16Brentuximab Vedotin: Mode of Action

Ansell SM. Expert Opin Investig Drugs. 2011 Jan;20(1):99-105. Epub 2010 Dec 2.Brentuximab Vedotin: HL TrialChen et al (2010) undertook a pivotal phase II trial on patients (n=102) with refractory or relapsed HL All had previously received an ASCT and the median number of prior chemotherapy regimens was 4

More than 70% had primary refractory disease and 39% were refractory to most recent prior therapy excluding ASCT

Chen R, Gopal AK, Smith SE, et al. Results of a pivotal phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsedor refractory hodgkin lymphoma [abstract #283]. American Society of Hematology Annual Meeting 2010Brentuximab Vedotin: HL Trial Results:

Median treatment time was 27 weeks

Median number of cycles was 9

Overall response rate was 75%

Reduction in the tumor size was evident in 95% of patients

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 [abstract #283]. American Society of Hematology Annual Meeting 2010

Brentuximab Vedotin: HL Trial% of PatientsBrentuximab Vedotin: ALCL Trial Sustov et al (2010) undertook a phase II study on patients with systemic ALCL (n=58)

Results have been reported on the first 30 patients Patients had a mean of two prior chemotherapy regimens and eight (27%) had failed ASCT Primary refractory disease was present in 19 (63%) and 16 (53%) had not responded to the most recent prior therapy

Shustv AR, Advani R, Brice P, et al. Complete remissions with brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large cell lymphoma [abstract #961]. American Society of Hematology Annual Meeting 2010Brentuximab Vedotin: ALCL Trial Objective response rate was 87%

Results:

Complete remission was achieved in 57% of patients (n = 17)

Partial remission was seen in 30% of patients (n = 9)

A reduction in tumor size was observed in 97% of patients

Mean time to objective response rate was 6 weeks

Duration of objective responses ranged from 4-36 weeks

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 [abstract #283]. American Society of Hematology Annual Meeting 2010

Brentuximab Vedotin: ALCL Trial% of PatientsFDA Approves Adcetris (Brentuximab Vedotin)Early clinical data suggest that patients who received Adcetris for Hodgkin lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy.

Adcetris is the first new FDA-approved treatment for HL since 1977 and the first specifically indicated to treat ALCL.

Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDAs Center for Drug Evaluation and Research.http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm268781.htm