Proteasome Inhibitors - Immunomodulatory Agents - IMiDs


Novel Agents

Novel agents are newer drugs that work in different ways than cytotoxic chemotherapy.
Proteasome inhibitors and immunomodulatory drugs (IMiDs®, Celgene) are novel agents that currently form the backbone of treatment for multiple myeloma.

Proteasome Inhibitors

Proteasome inhibitors work by blocking the function of proteasomes, whose role is to break down proteins in both healthy and cancerous cells. As a result of proteasome inhibition, proteins accumulate, interfering with the growth of cells, especially cancer cells. The slowdown in growth eventually leads to the death of the myeloma cells.

Approved Drugs

The first proteasome inhibitor to receive FDA approval was Velcade® (bortezomib, Takeda Oncology). When used in combination with IMiDs, this drug has proven to be highly effective.

In 2012, another proteasome inhibitor, Kyprolis® (carfilzomib, Onyx Pharmaceuticals, an Amgen subsidiary), was approved for patients who have received at least two previous rounds of treatment, including Velcade and an IMiD, and whose disease had progressed within 60 days of their last treatment.

These drugs are administered via injection into a vein (intravenously).

In 2015, a third proteasome inhibitor, Ninlaro® (ixazomib, Takeda Oncology), was approved for use in combination with Revlimid® (lenalidomide, Celgene) and low-dose dexamethasone in patients who have received at least one prior therapy. Unlike Velcade and Kyprolis, Ninlaro is taken orally.

In Development

One more proteasome inhibitor, oprozomib (Onyx Pharmaceuticals, an Amgen subsidiary), also taken orally, is in the pipeline, but it is not as far along.

Immunomodulatory Agents

Immunomodulatory agents, or IMiDs, have become a key part of the treatment regimen for multiple myeloma. They work by stimulating natural killer cells and activating T cells, reducing the growth of myeloma cells.

Approved Drugs

Thalomid® (thalidomide, Celgene) was the first drug in this class to be approved by the FDA, but it has been supplanted by the second generation of this compound, Revlimid, which is taken orally. Revlimid paired with Velcade has proved to be a winning combination.

Revlimid is also being used as maintenance therapy after upfront treatment. Most studies show a significant improvement in progression-free survival with this approach

Pomalyst® (pomalidomide, Celgene), the newest IMiD, is the most potent of the three. Given orally, it is reserved for patients who have received at least two prior therapies, including Revlimid and Velcade, and show disease progression within 60 days of their last therapy.