Phase II results of VELCADE in patients with aggressive lymphoma published in Journal of Clinical Oncology

Millennium: The Takeda Oncology Company today announced that Phase II results of a clinical trial examining VELCADE^® (bortezomib) in patients with previously untreated aggressive lymphoma were published in the Journal of Clinical Oncology. The study was designed to examine the efficacy of VELCADE in combination with the current standard of care (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; R-CHOP) in 76 patients with two aggressive subtypes of lymphoma: mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL).

“These data were part of the foundation for two ongoing randomized trials that evaluate VELCADE specifically in patients with this NF-κB dependent subtype of DLBCL”

Subsets of these tumors exhibit NF-κB activation. In this trial, VELCADE-R-CHOP was also evaluated for efficacy in the genomically defined subtype of DLBCL called non-germinal center B-cell (non-GCB) lymphoma. Prior studies have indicated that patients with non-GCB type tumors do not respond well to R-CHOP therapy due to the activation of the NF-κB pathway.

The endpoints of the Phase II trial included progression-free survival (PFS), response rate and overall survival (OS).

Highlights include:

• Among 35 evaluable DLBCL patients overall response rate was 100 percent, and the complete response rate was 86 percent
• After a median follow-up of 51 months, two-year PFS in DLBCL patients was 64 percent and two-year OS was 70 percent; median PFS and OS had not been reached
• No survival differences were observed between the GCB and the typically poor prognostic non-GCB subtypes
• Among 32 evaluable MCL patients, the overall response rate was 91 percent, and the complete response rate was 72 percent
• After a median follow-up of 34 months, two-year PFS in MCL patients was 44 percent and two-year OS was 86 percent; median PFS was 23 months, and median OS had not been reached
• The most common adverse events of any grade in the study were anemia (79 percent), thrombocytopenia (78 percent) and neutropenia (55 percent)
• The most common adverse events of grade 3 or higher were neutropenia (41 percent), thrombocytopenia (25 percent) and febrile neutropenia (17 percent)

"The growth of the non-GCB subtype of DLBCL depends on the activity of the NF-κB survival pathway, which is one of the pathways known to be inhibited by VELCADE. The concept of this trial was to test proteasome inhibition as a means to intervene in a critical lymphoma survival pathway," said John Leonard, M.D., Center for Lymphoma and Myeloma, Weill Cornell Medical College and principal investigator of the study. "Prior studies have indicated that even with R-CHOP therapy, which is the current standard of care in DLBCL, the non-GCB patients have inferior survival. Thus, we are encouraged to see the survival results from this study for this particular high-risk population."

"These data were part of the foundation for two ongoing randomized trials that evaluate VELCADE specifically in patients with this NF-κB dependent subtype of DLBCL," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "The U.S.-based PYRAMID study compares standard of care (R-CHOP) to VELCADE-R-CHOP in patients defined as non-GCB by a central laboratory. Additionally, our Phase III study examining a VELCADE based combination in previously untreated MCL includes an assessment of the NF-κB pathway status in each patient."

"This study adds to the growing body of evidence supporting the importance of VELCADE in subtypes of non-Hodgkin lymphoma with survival pathways involving NF-kB," said Sven De Vos, M.D., Ph.D., UCLA Medical Center.

VELCADE is currently approved for use in patients with multiple myeloma and relapsed MCL.