Last Updated: 2010-02-02 16:12:53 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The proteasome inhibitor bortezomib (Velcade) is effective in patients with follicular lymphoma and other indolent non-Hodgkin's lymphomas, according to a report in the January 12th issue of Clinical Cancer Research.

Approved for managing mantle cell lymphoma, bortezomib has shown an inconsistent pattern of activity across many subtypes of lymphoma, the authors explain, and its activity in follicular lymphoma has been a subject of controversy.

Dr. Owen A. O'Connor from the College of Physicians and Surgeons, Columbia University, New York, and colleagues investigated the activity of bortezomib monotherapy in 77 patients (69 assessable for response) with mantle cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), marginal zone lymphoma, or Waldenstrom's macroglobulinemia.

The overall response rate was 45% (40% on an intention-to-treat basis).

Nine of 18 patients with follicular lymphoma achieved a major response, including 4 with complete remission. Three of 8 patients with marginal zone lymphoma attained a partial remission; 1 of 9 patients with Waldenstrom's macroglobulinemia had stable disease; and 1 of 6 patients with SLL/CLL responded to treatment.

The median time to response was 11 to 12 weeks for patients with follicular lymphoma, compared with 4 weeks for patients with mantle cell lymphoma and all other subtypes of non-Hodgkin's lymphoma.

The overall progression-free survival was 4.75 months, the researchers note, compared with 9.8 months for the line of prior chemotherapy just before entry into this study.

Patients entering the study with refractory disease did worse than patients with relapsed disease, but the difference was of only borderline significance (p = 0.06).

There were no major hematologic toxicities besides lymphopenia and thrombocytopenia, and there were no opportunistic infections, but electrolyte abnormalities were common.

"These data suggest bortezomib has significant single-agent activity in patients with follicular lymphoma, and that longer durations of treatment may improve overall response," the authors say.

They add that theirs is the first report to suggest "that the time to treatment response may be one of the most important determinants of activity" for bortezomib in these patients.

The delayed response may be due to "the immunomodulatory effects of bortezomib on the lymphoma node microenvironment," they speculate.

"Future directions focused on understanding the merits of bortezomib in the indolent lymphomas will continue to explore how best to combine the agent with other known drugs used for these diseases," the investigators add.

Millennium Pharmaceutical, which manufactures bortezomib, provided commercial research grant support and an honorarium to Dr. O'Connor.

Clin Cancer Res 2010;16:719-726.