What to Expect: Targeted Therapies

Targeted therapy is a type of cancer treatment that specifically targets the molecules that benefit cancer cells in order to block those cells from growing, dividing, and spreading. These therapies cause cancer cell death and (mostly) leave the noncancerous cells alone. Because cancer cells produce different proteins, or a higher amount of certain proteins than normal cells do, researchers have been able to create drugs that can specifically kill cancer cells while sparing normal cells.

Targeted therapies are sometimes the product of a process termed “rational drug design,” in which researchers first understand the biological mechanisms that cancer cells use to grow and divide. Scientists uncover a molecule that can serve as a target for a drug. For example, the MMRF has been instrumental in the identification of a mutation that occurs in the BRAF gene of some myeloma patients, called V600E. When BRAF is mutated, it increases cell growth. Therefore, researchers sought to investigate drugs that would target BRAF mutations to see if they would be effective against BRAF-mutated tumors. The drug combination trametinib (Mekinist®) plus dabrafenib (Tafinlar®) has been approved to treat BRAF V600E-mutated melanoma and is currently being studied for myeloma. The MMRC, the collaborative clinical group of the MMRF, recently initiated a phase 2 trial to evaluate this combination therapy for BRAF-mutated myeloma.

Two main types of targeted therapy are used for multiple myeloma, antibodies and small molecule inhibitors.

Small molecule inhibitors
Small molecule inhibitors can easily travel into cells to reach their targets. These drugs can be injected into a vein (intravenously), into the abdominal cavity (intraperitoneally) or can be given as capsules taken orally.

Proteasome inhibitors
Proteasomes help the cell dispose of old proteins so they can be replaced by newer versions. They are essentially the trash disposal system of the cell. Proteasome inhibitors prevent cancerous plasma cells from “taking out the trash.” The old proteins pile up, interfering with cell functions, which causes the cancer cells to die. The following three different proteasome inhibitors are approved for treatment of myeloma:

Velcade® (bortezomib)
An intravenous (IV) or intraperitoneal (IP) drug that is given to patients as a first-line treatment, as well as for patients with relapsed disease. Velcade is often given in combination with other drugs and can be given to patients who have previously received Velcade.

Kyprolis® (carfilzomib)
An IV drug (either in combination or alone) given to patients who have previously received at least one other treatment for myeloma.

Ninlaro® (ixazomib)
An oral drug (used in combination with another drug) that is given to patients who have previously received another treatment for myeloma.

HDAC inhibitor
Some myeloma cells make too much of the histone deacetylase (HDAC) protein. This allows the malignant cells to grow and divide quickly. An HDAC inhibitor, such as the one below, targets this protein and inhibits its function, causing cell death. The following HDAC inhibitor has been approved for use in multiple myeloma:

Farydak® (panobinostat)
An oral drug given in combination with Velcade and dexamethasone to patients who have received at least two other treatments for myeloma.


Monoclonal antibodies are a type of protein that attach to specific proteins on the surface of cancer cells. The following two drugs in this class are given intravenously:

Darzalex® (daratumumab)
An antibody targeting the CD38 protein on myeloma cells. Darzalex works by binding to and “tagging” myeloma cells, thereby directly killing myeloma cells and also helping the immune system to recognize myeloma cells so they can be killed. It is used in combination with Revlimid and dexamethasone or with Velcade and dexamethasone in patients who have received at least one prior treatment for multiple myeloma, or is used alone in patients who have received at least three prior treatments.

Empliciti™ (elotuzumab)
An antibody targeting the SLAMF7 protein on myeloma cells. Empliciti works by” tagging” the myeloma cells and stimulating the immune system so that the immune cells can recognize myeloma cells and kill them. It is used in combination with Revlimid and dexamethasone in patients who have received at least one prior treatment for multiple myeloma.

To learn more about targeted therapies for myeloma, visit the following resources:


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