After a multiple myeloma diagnosis, your doctor will work with you to develop a treatment plan. Typically, this will involve first-line treatments commonly prescribed to help control myeloma, slow disease progression, and reduce or reverse complications.
However, myeloma cells can become resistant to treatment. If myeloma doesn’t respond or stops responding to treatment, it’s known as refractory myeloma. If you develop refractory myeloma, it’s important to know what to expect and what your next treatment options are.
In multiple myeloma, plasma cells (a type of white blood cell) grow rapidly and abnormally, causing damage to the bone marrow. Everyone who gets a diagnosis of myeloma is prescribed a first-line treatment regimen aimed at reducing the number of myeloma cells in the body while preventing damage to the organs.
The standard first-line treatment option involves triplet combinations of chemotherapy, immunomodulatory drugs, and proteasome inhibitors (PIs). This is known as induction therapy.
The most common combination of drugs used for induction therapy is lenalidomide (Revlimid), bortezomib (Velcade) and the corticosteroid dexamethasone.
Other combinations include:
After induction therapy, you may also undergo an autologous bone marrow transplant. This procedure uses your own healthy cells to replace the cancerous marrow destroyed during induction therapy.
While these initial therapies may be effective for some time, eventually most people with myeloma will relapse, meaning symptoms will return or worsen. If your doctor suspects your treatment plan is no longer working, they will run a series of tests. These may include blood work to look for the presence of M protein — an abnormal protein secreted by myeloma cells — and measure calcium levels, and a bone marrow biopsy to look for myeloma cells. They may also perform minimal residual disease testing, which looks at blood or bone marrow samples. These extremely sensitive tests can detect whether you need to restart treatment or try another therapy.
Once a treatment no longer works against myeloma, the myeloma is considered to be refractory. A person may have had a complete response (no remaining signs of myeloma in the body) to the first-line treatment, but over time their myeloma became resistant.
If you’re diagnosed with refractory myeloma, your doctor will discuss your next treatment options with you. These will depend on a few factors, including what treatment plan was used for first-line therapy, along with your age and overall health. Some treatments — like high-dose chemotherapy — are more intense than others and have side effects that may be difficult for some people to handle. The median age of myeloma diagnosis is 70 years, and age can affect organ function and overall health.
To determine which treatment options are best after a relapse, certain tests are recommended, including:
Together, you and your doctor consider all of the results and form a new treatment plan.
While not widely used currently, genetic testing is being studied as a way to monitor treatments for those with multiple myeloma. The MATCH screening trial is a phase 2 clinical trial examining genetic testing to influence treatment decisions for refractory myeloma, along with lymphoma and other cancers. Researchers hope someday genetic testing can be a tool for developing better treatment plans for people with refractory cancers.
Receiving a refractory myeloma diagnosis can be overwhelming, but there are several other treatment options available to help. These include other types of PIs, immunomodulatory drugs, and immunotherapy, along with newer treatments to help control myeloma.
For those who were treated with thalidomide or lenalidomide and have progressed to refractory myeloma, there is a third option available. Pomalidomide (Pomalyst) is similar to these medications, but it can be used in combination with dexamethasone to treat refractory disease.
In cases where first-line PIs like bortezomib fail, there are a few other options. Ninlaro (a formulation of ixazomib) is an oral PI approved by the U.S. Food and Drug Administration (FDA) to treat refractory myeloma. It’s often combined with dexamethasone and lenalidomide.
Carfilzomib (Kyprolis) is another PI that can be given alone to people with refractory myeloma who were treated with at least one other therapy. It can also be used in a few different combinations to treat refractory myeloma after one to three other lines of therapy. These combinations include:
While not yet approved, marizomib is a third PI undergoing clinical studies for treating myeloma. It shows early promise, and trials continue to investigate it.
Chimeric antigen receptor (CAR) T-cell therapy is a cancer treatment in which the T cells from your immune system are changed to better recognize cancer cells. These changed cells are then infused back into your bloodstream to help fight cancer.
In early 2021, the FDA approved Abecma — a formulation of idecabtagene vicleucel — to treat refractory myeloma in people who have tried four or more lines of treatment — including PIs, immunomodulatory drugs, and monoclonal antibodies. It is specialized to each individual with myeloma, using their own T cells. Studies show that 28 percent of people achieved complete response on idecabtagene vicleucel, and 65 percent of those maintained the response for at least 12 months.
Monoclonal antibodies are specialized antibodies that have been engineered to recognize certain markers on immune cells and cancer cells.
Elotuzumab (Empliciti) was the first FDA-approved monoclonal antibody for treating relapsing/refractory multiple myeloma. It is not prescribed on its own in treatment. Instead, it’s used in two different combination therapies to treat refractory myeloma. The first is with dexamethasone and lenalidomide to treat people who have already received one to three lines of treatment. The second is with dexamethasone and pomalidomide to treat those who have received at least two therapies (lenalidomide and PIs).
While daratumumab is often used as first-line therapy, the drug can also be used to treat those with refractory myeloma that is resistant to both PIs and immunomodulatory drugs. It’s administered alone to treat refractory myeloma after a person has tried at least three lines of therapy (including an immunomodulatory drug and PIs).
The FDA has approved Sarclisa, a formulation of isatuximab-irfc, to treat refractory myeloma in people who previously received one to three lines of treatment. It’s combined with dexamethasone and carfilzomib to be as effective as possible.
Outside of the main drug classes used to treat multiple myeloma, panobinostat (Farydak) is another option. This histone deacetylase inhibitor is combined with dexamethasone and bortezomib to treat myeloma in people who were previously treated with an immunomodulatory drug and bortezomib.
While there are many therapies currently available, researchers and doctors are always looking for the next effective refractory myeloma treatment. These include novel drugs that are not yet approved or new combinations of available drugs.
Currently, several clinical trials are investigating refractory myeloma treatments. Existing drugs like selinexor, dexamethasone, and carfilzomib are being studied in combination, as well as new drugs like ABBV-453.
If you’re interested in learning more about ongoing clinical trials, you can take a look at those supported by the National Cancer Institute or ask your hematology specialist. Clinical trials are available for all stages of myeloma, including refractory myeloma.
Read more about new treatment options for relapsed or refractory myeloma.
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