Myeloma is characterized by the malignancy of a type of white blood cell (WBC) called B cells. The most common type of this blood cancer is multiple myeloma, which affects areas in the body where the bone marrow is active — including the spine, skull, pelvis, rib cage, and areas around the shoulders and hips.
One of the most common therapies used to treat myeloma are immunomodulatory drugs, or IMiDs. These include Thalomid (thalidomide) and its derivatives, Revlimid (lenalidomide) and Pomalyst (pomalidomide). All have been developed and marketed by Celgene.
IMiDs are used to treat people newly diagnosed with multiple myeloma. They also serve as as a maintenance therapy for patients who have undergone an autologous hematopoietic stem cell transplant (ASCT), or for individuals whose disease has returned following treatment.
More about myeloma
B cells are a type of WBC that produce antibodies to fight off bacterial and viral infections. Myeloma cells are malignant B cells that have the same characteristics. These cells:
- Grow out of control.
- Affect the ability of the bone marrow to produce different types of blood cells, including red blood cells (RBCs).
- Secrete high levels of proteins in the blood and urine that can cause kidney disease.
- Accumulate in different organs, such as the lungs and the liver, and affect their function.
- Weaken bones, which results in severe bone pain and may lead to fractures.
How do IMiDs work?
The exact mechanism of action of IMiDs is not known, but they are though to work in multiple ways. They are known to:
- Suppress the growth of myeloma cells.
- Kill myeloma cells.
- Improve the function of normal immune system cells such as T cell and natural killer (NK) cells, which have the natural ability to identify and kill malignant myeloma cells.
- Suppress the formation of new blood vessels, called angiogenesis, which is required for the survival, growth, and spread of myeloma cells.
- Decrease the production of cell signaling molecules that promote inflammation.
- Change the bone marrow in a way that is non-conducive for the growth and survival of myeloma cells.
IMiDs to treat myeloma
The primary treatment strategy for newly diagnosed myeloma patients is a combination of a proteasome inhibitor like Velcade (bortezomib) with an IMiD and the steroid dexamethasone. Thalomid, Revlimid, or Pomalyst are often prescribed as the IMiD. However, second-generation IMiDs, namely Revlimid and Pomalyst, are less toxic and more effective than Thalomid.
This medicine is the synthetic derivative of the amino acid glutamic acid. Amino acids are building blocks of proteins. Thalomid was first approved for the treatment of myeloma in 1998. Now, first-in-class derivatives of thalidomide such as Revlimid and Pomalyst are preferred because of better efficacy and lower side effects. Thalomid, however, is a good alternative to lenalidomide for myeloma patients with low blood cell counts.
Approved by the U.S. Food and Drug Administration (FDA) in 2006 for use in combination with dexamethasone, Revlimid was originally cleared only for people with multiple myeloma who had received at least one prior therapy. This was expanded, in 2016, to include newly diagnosed patients who are not eligible for ASCT. The FDA approved Revlimid as maintenance therapy for people with multiple myeloma following ASCT in 2017.
The IMiD Pomalyst has a hybrid structure between thalidomide and lenalidomide. It was approved by the FDA in 2013 for use in combination with low-dose dexamethasone for people with multiple myeloma who had previously been treated with Revlimid and a proteasome inhibitor, but whose disease had returned. In November 2016, the FDA approved a combination therapy that includes the monoclonal antibody daratumumab, pomalidomide, and dexamethasone for multiple myeloma patients who have received at least two prior therapies, including Revlimid and a proteasome inhibitor.
The common adverse effects of IMiDs include:
- life-threatening birth defects, or the possible death of the newborn if parents take the medication at the time of conception or during pregnancy
- risk of blood clots, including life-threatening blood clots that can cause deep vein thrombosis and pulmonary embolism (blood clots in the arteries of the lungs)
- leukopenia, or low WBC counts
- anemia, or low RBC counts
- peripheral neuropathy, or the impairment of the nerves of the hands, arms, legs, and feet, which can cause tingling sensations or pain
Last updated: Nov. 7, 2019
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