First Treatment for Multiple Myeloma — Combination Therapy

You have been diagnosed with multiple myeloma and are about to undergo the first phase of treatment. The strategy today is to use multiple drugs.

According to Dr. Paul Richardson, Director of Clinical Research at  the Multiple Myeloma Center at Dana-Farber Cancer Institute, “It’s very important to sort of combine strategies to do more, with different approaches put together in a rational and safe fashion,” to address the unique complexities of the cancer. He likens these strategies to attack myeloma cells to the different sectors of military. “A good metaphor is to think of it as the army, navy, coast guard, and marines as a sort of stratagem to deliver that much more to take on myeloma full tilt.”

During the first stage of therapy, the induction phase, patients are enrolled in a combination therapy known as RVD consisting of:

• Revlimid (lenalidomide): This has two primary functions. Firstly, it directly kills myeloma cells. Secondly, it is has an effect on the immune system. The drug activates your immune system to target cancer cells and kill them like they would any other infection.
• Velcade (bortezomib): This targeted therapy disrupts the mechanism by which cancer cells break down antibodies. You don’t want too many antibodies within the cell because an excess will eventually cause the cells to die.
• Dexamethasone: This is a steroid drug that prevents inflammation and associated pain from myeloma, and it can even help kill myeloma cells at high doses, especially early in care

What makes Velcade effective is it can target what is a good function in the body and turn it into a function that will destroy cancer cells. Velcade targets proteasomes. The function of proteasomes is to do something good. They break down proteins in healthy cells because too many proteins can destroy a cell. Proteasomes are kind of like the body’s garbage disposal for proteins. But there are also proteasomes  in cancer cells. When Velcade  is given, the drug in effect sends a message to the proteasomes saying “You know that garbage disposal you have of eliminating proteins? We want you to cut back on doing that in cancer cells.” And when the proteasomes cutback on their antibody disposal function in the cancer cell, antibodies build and  build until the cancer cell dies.

And since myeloma cells produce many more antibodies compared to healthy cells, they are particularly susceptible to Velcade. Dr. Sagar Lonial, Chief Medical Officer at the Winship Cancer Institute of Emory University explains, “When we think about using a drug that blocks the garbage disposal, that’s really important in myeloma because there is so much antibody produced that without that garbage disposal, the cell dies. So, blocking it is a key unique factor in myeloma that we can go after.”

The combination of these three drugs has been shown to be highly effective as the first treatment myeloma patients receive. So much so that doctors agree it should be the standard of care.

One cycle of RVD therapy takes three weeks to complete, and treatment typically lasts anywhere from 3-6 cycles. Side effects include diarrhea, feeling tired, nausea, vomiting, loss of appetite, swelling in the arms or legs, fever, and weakness. You may be wondering, will I still be able to work while on treatment? Will I be bed-ridden? The good news is that not much will change from your life. According to Dr. Lonial, patients could be able to conduct their daily lives as normal while on RVD therapy. “I typically tell patients that, if they are young, and young for me is 30-65, right? I have patients that have continued to work and do what they do—as attorneys, as physicians, as other professionals—throughout their first four cycles of induction therapy.”

However, not all patients respond this favorably to RVD treatment. For these patients, alternative strategies are used. Lonial explains, “There are other patients who experience side-effects early on, and we usually know that in the first cycle, that cause us to limit treatment or to modify treatment.” Regardless of how patients respond to the induction phase, “a goal is to maintain quality of life.”

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