Advances in treatment for multiple myeloma have improved survival rates over the last 3 decades. But researchers are still figuring out the best treatments for high-risk multiple myeloma. It can’t be cured, so the goal is symptom-free survival balanced with treatment side effects. Here’s what you need to know.
What Is High-Risk Multiple Myeloma?
Multiple myeloma is typically divided into two categories: standard-risk or high-risk. That’s based on four factors:
- Gene mutations or changes
- The amount of a protein, beta-2-microglobulin, in your blood
- The amount of albumin in your blood
- The amount of lactate dehydrogenase (LDH) in your blood
The specific gene changes are:
- Losing a piece of chromosome 17
- A translocation, or exchange of materials, from chromosome 4 to 14
- An exchange of materials between chromosomes 14 and 16.
About a quarter of all cases are high-risk.
How Is High-Risk Multiple Myeloma Treated?
Your doctor will likely want to start treatment ASAP. It’ll be more aggressive than therapies for standard-risk multiple myeloma.
The hope is to see what experts call a complete response. That means:
- No monoclonal protein in your blood or urine
- No large groups of plasma cells outside your bone marrow
- The number of plasma cells in the bone marrow isn’t high.
Options include:
Daratumumab and hyaluronidase-fihj (Darzalex Faspro). Your doctor may recommend you take this drug combination if you have high-risk smoldering multiple myeloma. The drug is injected under the skin of your abdomen and can help prevent smoldering multiple myeloma from developing into active myeloma.
Clinical trials. Experts often suggest that people with high-risk multiple myeloma take part in clinical trials.A clinical trial is a safe way to study how well new treatments or new combinations of existing treatments work. You can find information about clinical trials near you at: https://www.cancer.gov/about-cancer/treatment/clinical-trials.
If you don’t want to do a clinical trial or aren’t a good fit for one, you can try the medications used to treat standard-risk multiple myeloma. These are:
Bortezomib (Velcade),carfilzomib (Kyprolis), and Ixazomib (Ninlaro). These drugs are proteasome inhibitors. Proteasomes themselves break down protein in cell. They are very active in multiple myeloma cells, which make a lot of protein. These drugs stop proteasomes from doing their job. So proteins build up and myeloma cells die. Bortezomib and carfilzomib are usually given as a shot under the skin (subcutaneously). Ixazomib is given as a capsule. Side effects include nerve damage and a higher risk of infection.
Lenalidomide (Revlimid). This is an immunomodulator. It uses your body’s own immune system to fight myeloma cells. It’s taken as a pill. Other options in this class of drugs include pomalidomide (Pomalyst) and thalidomide (Thalomid). Since they may cause severe birth defects, you can’t use them if you’re pregnant.
Dexamethasone. This is a steroid that kills myeloma cells when given in high doses. It’s given as a shot in your muscle or through an IV in your vein. The combination of an immunomodulator and a steroid raises your risk of forming blood clots. Your doctor may recommend that you take aspirin, or prescribe a blood thinner.
Daratumumab (Darzalex). This drug may be added. It’s a monoclonal antibody that kills myeloma cells directly and tags the CD38 protein they make. This helps your immune system recognize and attack them. Daratumumab is given as a shot under the skin or through an IV into your vein.
Iberdomide (Zenebexus) . This drug belongs to a new drug class known as cereblon E3 ligase modulatory drugs (CELMoDs). These are medications that target specific proteins in cancer cells and break them down, helping to stop cancer cell growth and causing the cells to die. Iberdomide was recently FDA-approved in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) for treatment of multiple myeloma in adults who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. If you have certain high-risk genetic changes found in your plasma cells, you might receive Iberdomide as a part of your treatment plan for relapsed/refractory multiple myeloma.
Is a Stem Cell Transplant the Best Option for High-Risk Multiple Myeloma?
It may be another option if you don’t want to do a clinical trial or aren’t a good fit for one. Stem cell transplants are when healthy cells from another part of your body (or from someone else) are put into your bloodstream. They travel to your bone marrow and (hopefully) start to make new blood cells.
Stem cell transplants have considerable risks and complications, so it’s not a good idea for everyone. In Europe, they’re usually only offered to people under the age of 65. The U.S. doesn’t use a strict age limit. Your doctor will decide based on your age and overall health.
Before the transplant, your stem cells are collected, frozen, and stored for use in the transplant. High-dose chemotherapy is given during the transplant that kills the myeloma cells. Once the chemotherapy is done, an infusion of your stem cells is given. These stem cells travel to the bone marrow and start producing new blood cells. Once you’re done, the doctor will probably want you to get the stem cell transplant right away to try to keep your disease from getting even worse.
Your doctor may also recommend a tandem transplant. That’s when you do the transplant process again, usually after three to six months. Studies are ongoing to help determine if tandem stem cell transplants increase survival in people with high-risk multiple myeloma.
