A drug that has become a mainstay of multiple myeloma treatment may outperform alternative therapies in re-establishing the immune system of patients who have received stem cell transplants from unrelated, partially matched donors, according to early clinical trial results to be presented by Dana-Farber Cancer Institute investigators at the American Society of Hematology's (ASH) annual meeting on Sunday, Dec. 6 (Abstract 48, Ernest N. Morial Convention Center, Room 243-245, 5:45 pm CT).
The trial was designed to determine whether the drug bortezomib (trade name Velcade), when added to routine agents (tacrolimus, methotrexate), can improve control of graft-versus-host disease (GVHD) and improve immune system recovery following a transplant from a mismatched-unrelated donor. GVHD is a common and potentially severe side effect of blood-forming stem cell transplants, in which donor immune cells attack normal patient cells and tissues. GVHD is more frequent in patients receiving transplants from mismatched-unrelated donors (in comparison with matched-related donors).
Based on bortezomib's effect in preclinical models, and in multiple myeloma patients who have received donor stem cell transplants, Dana-Farber's John Koreth, MBBS, DPhil, and colleagues theorized that it could help control the overactivity of immune cells responsible for GVHD in stem cell transplant patients.
Bortezomib inhibits the activity of antigen-presenting cells, which help initiate the immune attack in GVHD, and reduces activity of an important protein called nuclear factor-B in T cells, which undertake the immune attack. In preclinical studies, bortezomib has been shown to selectively deplete T cells that can target patients' normal cells. Mouse transplant studies have shown that early administration of bortezomib protects against GVHD without reducing the transplanted stem cells' ability to settle in the bone marrow.