Proteasome inhibitors and
immunomodulatory drugs (
IMiDs) have demonstrated clinical potential as novel
therapies for
non-Hodgkin lymphoma (NHL).
Bortezomib, a
peptide aldehyde derivative that inhibits the
proteasome by binding directly to its active sites, is the most extensively studied agent in the clinical setting. Single-agent
bortezomib is effective in several lymphoid
malignancies, and is recommended for second-line treatment of
mantle-cell lymphoma (MCL). Ongoing trials are investigating the combination of
bortezomib with
chemotherapy, and with agents that target Bcl-2
proteins. Although
proteasome inhibitors are potentially potent anti-
tumor drugs, the pleotropic nature of their
biological effects means that further research is required to elucidate the optimal combinations, doses and schedules. In addition to
proteasome inhibitors, the
IMiDs, such as
lenalidomide, have the potential to improve outcomes for patients with NHL. These drugs inhibit cell growth and proliferation by several mechanisms, including blocking the effect of
growth factors and stimulating T cells and natural killer cells.
Lenalidomide is particularly effective in
lymphoproliferative disorders such as
multiple myeloma, and is active in patients with various forms of NHL, with a favourable side-effect profile. Complimentary clinical and pharmacological features suggest that
lenalidomide may be effective when combined with
monoclonal antibodies. Ongoing and future studies will provide further information.