• Immunotherapy is a newer type of cancer treatment that can modify the immune system to target myeloma cells for destruction.
• Several monoclonal antibody therapies are approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma.
• New forms of immunotherapy, such as CAR-T cell therapy, are under development for multiple myeloma.

Traditionally, multiple myeloma treatment relies on chemotherapy drugs and radiation. However, new discoveries in the field of immunotherapy are now expanding treatment options for people living with myeloma. Immunotherapy modifies the immune system to target and fight cancer cells.

In multiple myeloma, cancerous myeloma cells multiply out of control. Traditional chemotherapy treats multiple myeloma by targeting all rapidly dividing cells in the body. But chemotherapy also destroys healthy cells that divide rapidly, causing toxicity and harsh side effects. Immunotherapy can be used to target the immune system against the myeloma cells for more specific killing and less harsh side effects.

What Are Monoclonal Antibodies?

The immune system is an intricate collection of cells designed to fight infection and protect the body from foreign invaders. The immune system also conducts regular surveillance (known as immune surveillance) to identify and remove cancerous cells from the body.

Unfortunately, cancer cells are sometimes able to slip past immune surveillance and grow out of control. Many forms of immunotherapy focus on retargeting and reactivating the immune system against cancer.

The idea of using the immune system to fight cancer was first proposed in the late 19th century, but immunotherapies were not approved by the FDA until the late 20th century when monoclonal antibodies were first developed.

Antibodies are proteins made by a particular immune cell called a B cell. These antibodies have binding areas that allow them to attach to the specific cells they are made to target. Scientists have figured out how to make antibodies that specifically bind to certain molecules and cell types in the body. When a large number of antibodies are produced with the same target, it is referred to as a monoclonal antibody.

A monoclonal antibody works by binding to its target and then blocking the action of the bound molecule. It may also induce the molecule’s destruction by the immune system. Other cells in the immune system will recognize the antibody and react to it by destroying the molecule or cell it is bound to.

FDA-Approved Immunotherapies for Multiple Myeloma

There are several immunotherapies approved by the FDA to treat multiple myeloma. Many of these are monoclonal antibodies that target proteins called cell receptors. Certain cell receptors are commonly displayed on the surface of myeloma cells.

Currently, the following monoclonal antibody therapies are approved for individuals with advanced multiple myeloma.

Darzalex

Darzalex (daratumumab) works by targeting the cell receptor known as CD38 on the surface of myeloma cells. While other cells in the body express CD38, myeloma cells display a very high density of these molecules on their cell surfaces. Once Darzalex binds to CD38 on the myeloma cell, it will attract immune cells known as natural killer cells to come and destroy the myeloma cell.

Sarclisa

Sarclisa (isatuximab-ifrc) works similarly to Darzalex. It recognizes CD38 on the surface of myeloma cells and recruits other immune cells, including natural killer cells, to come and kill the myeloma cell.

Empliciti

Empliciti (elotuzumab) targets a surface receptor of myeloma cells known as the SLAM family member 7 (SLAMF7). The SLAMF7 receptor appears in large numbers on myeloma cells, and it promotes the growth of myeloma cells. Empliciti has been shown to block the activity and growth promoted by SLAMF7 and target myeloma cells for destruction by natural killer cells.

Blenrep

Blenrep (belantamab mafodotin-blmf) is a monoclonal antibody attached to a cytotoxic (cell-killing) drug. This combination is known as an antibody-drug conjugate. The target of Blenrep is B-cell maturation antigen (BCMA), which is displayed on myeloma cells and normal B cells in the immune system. The antibody binds to a myeloma cell, allowing the cytotoxic drug to enter the cell and induce cell death. Blenrep also targets myeloma for destruction by other cells in the immune system, including natural killer cells.

Side Effects of Immunotherapy

Monoclonal antibodies are usually given intravenously (by IV). Monoclonal antibody therapy typically has less harsh side effects compared to chemotherapy. However, there is a risk of serious allergic reaction. Other side effects can include:

• Flu-like symptoms, such as muscle pain, weakness, fever, fatigue, and chills
• Nausea and vomiting
• Diarrhea
• Low blood pressure
• Headache
• Rash
• Eye damage

New Immunotherapies in Development

Additional monoclonal antibodies and antibody-drug conjugates are being developed for the treatment of multiple myeloma. Chimeric antigen receptor (CAR)-T cell therapy is also under development for myeloma treatment. T cells are a type of white blood cell in the immune system that can directly kill an infected or cancerous cell. The activation of a T cell requires many steps to ensure the T cell recognizes and kills cancerous cells and does not kill healthy cells.

Scientists have found a way to bioengineer T cells to express a receptor, known as the chimeric antigen receptor, so the T cell can directly recognize and kill a cancer cell. The CAR actually uses a small portion of an antibody, known as the binding site, to recognize a surface receptor on the surface of the cancer cell. Then the CAR-T cell can recognize and kill the cancer cell without all of the steps needed to activate a normal T cell.

CAR-T cells are generated by collecting an individual's normal T cells and bioengineering them to express the CAR. The CAR-T cells are then returned to the body to fight the cancer. One of the advantages of CAR T-cell therapy is that CAR-T cells can sometimes live for a long time and fight off cancer even as new cancer cells are generated.

Currently, CAR-T cell therapies are in clinical trials for treating multiple myeloma. Targets for CAR-T cells in multiple myeloma include BCMA.

Talk With Others Who Understand

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References

1. 1. Cancer immunoediting from immune surveillance to immune escape — Immunology
   2. A Brief History of Immunotherapy — Targeted Oncology
   3. How is Immunotherapy for Multiple Myeloma Changing the Outlook for Patients? — Cancer Research Institute
   4. Current FDA-Approved Medications — International Myeloma Foundation
   5. CD38 Expression by Myeloma Cells and Its Role in the Context of Bone Marrow Microenvironment: Modulation by Therapeutic Agents — Cells
   6. Daratumumab induces mechanisms of immune activation through CD38+ NK cell targeting — Leukemia
   7. Isatuximab Acts Through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple Myeloma Cells — Frontiers in Immunology
   8. Soluble SLAMF7 promotes the growth of myeloma cells via homophilic interaction with surface SLAMF7 — Leukemia
   9. BCMA-targeted immunotherapy for multiple myeloma — Journal of Hematology and Oncology
   10. Multiple myeloma survivor grateful CAR T cell therapy clinical trial gives her another option — MD Anderson Cancer Center
   11. Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma — Journal of Hematology and Oncology
   12. CAR T Cell Therapy — National Cancer Institute
   13. Monoclonal Antibodies and Their Side Effects — American Cancer Society