Immunotherapy for Multiple Myeloma

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Immunotherapy is a type of treatment that helps your immune system fight disease. Recently approved immunotherapies for multiple myeloma offer more treatment options for this hard-to-treat blood cancer.
Myeloma is cancer of white blood cells that form in bone marrow. The job of white blood cells is to defend against disease. In myeloma, cancer cells crowd out normal cells and weaken your immune system. The immune system doesn’t recognize myeloma cells. That makes it easier for them to grow and spread.
Immunotherapies strip myeloma cells of the ability to hide in plain sight. And they keep myeloma from weakening the immune system.
Immunomodulating agents, targeted antibodies, and Chimeric antigen receptor (CAR) T-cell therapy are all immunotherapies that can help people with multiple myeloma. Stem cell transplant is also a common treatment.
This article discusses immunotherapies for multiple myeloma, how they work, and when they’re useful.

Immunomodulating agents

Immunomodulating agents
Immunomodulating agents are drugs that either stimulate or suppress your immune system in a nonspecific way. They’re also called immune system modulators. The three immunomodulating agents for multiple myeloma are:
Lenalidomide (Revlimid): Lenalidomide is used for all stages of multiple myeloma. It’s sometimes used as maintenance therapy if you’re in remission, but you might also take Revlimid following a stem cell transplant or other treatment.
Pomalidomide (Pomalyst): Pomalidomide is used for relapsed or refractory multiple myeloma. Pomalyst is also for people with high-risk multiple myeloma or kidney problems.
Thalidomide (Thalomid): Thalidomide may be used if you have low blood cell counts and can’t take other immunomodulating agents. According to the Myeloma Research Foundation, it’s rarely used today.
All three immunomodulating agents are daily oral medications. They’re often used in combination with other drugs in cycles of 21 to 28 days.
Read more about immune system modulators here.

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Targeted antibodies

Targeted antibodies
Antibodies are infection-fighting proteins made by the immune system. Monoclonal antibodies are lab versions of these proteins. Scientists design them to target specific proteins on the surface of cancer cells. Those used to treat myeloma are:
Daratumumab (Darzalex): Darzalex attaches to the CD38 protein on myeloma cells and helps your immune system see and destroy cancer cells. It’s useful in all stages of myeloma, alone or in combination with other drugs. An intravenous (IV) version and an injectable version (Darzalex Faspro) are available. The cycle of treatment depends on the specific combination of drugs.
Isatuximab (Sarclisa): Isatuximab attaches to the CD38 protein and helps the immune system see and kill cancer cells. It’s for people who have already tried at least two other treatments. You get it intravenously once every week or once every 2 weeks in 28-day cycles.
Elotuzumab (Empliciti): Elotuzumab targets a protein called SLAMF7. It prompts natural killer cells to activate and flag myeloma cells for destruction. It’s for people who have already tried other therapies. You get Empliciti intravenously once a week or once every other week in 28-day cycles.
There’s also a bispecific T-cell engaging antibody. That means it can bind to two different antigens at the same time:
Teclistamab (Tecvayli): This antibody targets the CD3 protein on T-cells and the BCMA protein on myeloma cells. It’s for people who have tried at least four other therapies that are no longer working. You get it by injection just under the skin, typically three times the first week, then once a week.
There are also drugs called antibody drug conjugates. They’re a combination of monoclonal antibodies and other cancer-fighting drugs.

CAR T-cell therapy

CAR T-cell therapy
CARs help T cells attach to specific proteins. This therapy involves taking T cells from your blood and altering them in a laboratory. In multiple myeloma, CAR T-cell therapies target the BCMA protein.
Using an IV line, your blood will run through a machine that removes T-cells. Then the blood will return to your body.
Next, you’ll need high-dose chemotherapy. This prepares your immune system for the treatment. Later, you’ll have the modified T cells infused back into your body. The modification will allow these T cells to see and attack myeloma cells. The T cells will also continue to multiply and strengthen your immune system.
This is a one-time therapy. The two CAR T-cell therapies approved for multiple myeloma are ciltacabtagene autoleucel (Carvykti) and idecabtagene vicleucel (Abecma).
These aren’t first-line therapies. They’re for people who have already had several other types of treatment.
Read more about CAR T-cell therapy here.

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Stem cell transplant

Stem cell transplant
According to the American Cancer Society, autologous stem cell therapy (ASCT) is a standard treatment for people with multiple myeloma. It’s a form of immunotherapy because it alters the immune system. It helps your body produce healthy new blood cells.
First, you get high-dose chemotherapy to destroy cancer cells. Then, doctors remove stem cells from your bone marrow or peripheral blood. Later, these stem cells are reinfused into your body to help your bone marrow produce healthy new blood cells.
ASCT is a common treatment for people with a new diagnosis or relapsed multiple myeloma. It’s usually a one-time therapy. In some cases, a doctor may recommend a tandem transplant. That means you have two autologous transplants 6 to 12 months apart.
Read more about stem cell treatments for multiple myeloma here.

Other treatments for multiple myeloma

Other treatments for multiple myeloma
A treatment plan usually involves a combination of two or three different kinds of therapies. Aside from immunotherapies, drug therapies include:
proteasome inhibitors
steroids
a nuclear export inhibitor called selinexor (Xpovio)
bisphosphonates for bone disease
Other multiple myeloma treatments are:
chemotherapy
radiation therapy
supportive care
Which therapies are right for you depend on how aggressive the cancer is and what treatments you may have already had. Your doctor will make a recommendation based on your health and personal preferences.
Read more about multiple myeloma treatment here.

Promising new immunotherapies for myeloma

Promising new immunotherapies for myeloma
Stem cell transplantation and immunomodulating agents have long been a mainstay of treatment. The first monoclonal antibodies gained approval in 2015, and the pace for immunotherapies is picking up.
New immunotherapies since 2021 for multiple myeloma include two CAR T-cell therapies and the first bispecific antibody. These therapies are fairly new, so researchers are still waiting on long-term data.
Research into other immunotherapies is ongoing. Some areas of interest are:
immune checkpoint inhibitors, which are already used to treat other types of cancer
next generation immunomodulators
new antibody-drug conjugates
new bispecific antibodies

Takeaway

Takeaway
Immunomodulating agents and stem cell transplantation have been around for decades. But recent advances in immunotherapy mean more options for people who have already tried other therapies for multiple myeloma.
Newer options include monoclonal antibodies, a bispecific T-cell engaging antibody, and CAR T-cell therapy. This cancer is difficult to treat, but immunotherapy is a promising area and the subject of ongoing research.

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