Immunotherapy is a promising and rapidly growing field in multiple myeloma treatment. What makes immunotherapy exciting is that it represents a totally new approach to myeloma treatment, using the body’s own immune system to fight myeloma.
But what exactly is immunotherapy? And how does it work?
Put simply, myeloma immunotherapy is the use of drugs and other approaches to help a patient’s immune system fight multiple myeloma. In healthy individuals, the immune system uses a number of specialized cells that circulate throughout the body looking for and destroying foreign invaders—for example, bacteria, viruses, and cancer cells. In patients with multiple myeloma, the immune system is suppressed, which increases the patient’s risk for infection and rapid tumor development. Myeloma immunotherapy “resets” the immune system—enabling the body to use its natural defenses to target and destroy myeloma cells.
There are different types of myeloma immunotherapy. Each uses a different approach to help the immune system:
- Antibody-based treatments use agents that recognize and target specific proteins that are found on myeloma cells. These agents can help the patient’s immune system identify and eliminate the targeted myeloma cells or they can help the immune system overcome the suppressive effects produced by the myeloma cells
- Cell-based treatments use immune cells taken from the patient or a donor to attack the myeloma cells directly or indirectly
- Myeloma vaccines boost the immune system’s ability to destroy myeloma cells
Two monoclonal antibodies—Darzalex and Empliciti—have already been approved for use in patients with multiple myeloma.
Darzalex, which targets a myeloma cell surface protein called CD38, is approved for use in patients who are newly diagnosed with myeloma and are not eligible for autologous stem cell transplant (ASCT). It is also used as part of combination therapy (that is, used with other drugs) for patients whose myeloma has relapsed or become refractory to treatment.
Empliciti targets a protein called SLAMF7, which is present not only on myeloma cells but also on a type of immune cell called natural killer (NK) cells. Empliciti makes it easier for the NK cells—whose job it is to fight invaders—to find and destroy myeloma cells. Like Darzlex, Empliciti has been approved as part of combination therapy for patients with relapsed or refractory myeloma.
Other monoclonal antibodies are in development. One of these is isatuximab, which also targets CD38 and is in late-stage clinical trials. Not only does isatuximab help boost the immune response to myeloma (like Darzelex), but it is also able to kill myeloma cells directly.
Another type of myeloma immunotherapy uses what is called an antibody-drug conjugate, which is a monoclonal antibody that has been combined with a cancer drug. The advantage to antibody-drug conjugates is that they combine the invader-targeting action of antibodies with the myeloma-killing ability of cancer drugs.
One antibody-drug conjugate currently being studied as a myeloma treatment is belantamab mafodotin. The monoclonal antibody portion of this agent targets a protein called B-cell maturation antigen (BCMA) that is found on the surface of myeloma cells. The drug component is called monomethyl auristatin phenylalanine (MMAF), which blocks myeloma cells from dividing. In clinical trials, belantamab mafodotin produced a rapid, deep and durable response in heavily pre-treated myeloma patients with relapsed or refractory multiple myeloma. It was also shown to be well tolerated.
Bispecific T-cell engagers (also known as BiTEs) are yet another type of myeloma immunotherapy. BiTEs consist of two antibody fragments that have been fused together: one antibody fragment binds to a protein found on myeloma cells, and the other antibody fragment binds to—and thus activates—a protein found on the surface of an immune cells called T cells. By targeting both myeloma cells and T cells, BiTEs help the T cells kill the myeloma cells.
A BiTE called AMG420 is currently being studied as a treatment for myeloma. This BiTE targets BCMA. In an early-phase clinical trial, AMG420 produced a response in 31% of patients was associated with relatively manageable side effects.
In addition to these antibody-based treatments, engineered immune cells are generating interest in myeloma treatment, due to their potential for eliciting responses in most patients, including those in which the myeloma relapsed despite many prior therapies. In these cell-based therapies—collectively referred to as adoptive cell therapies—immune cells (mostly T cells) obtained from the patient’s own blood are multiplied in a laboratory, engineered to be more effective at targeting and removing cancer cells, and then re-introduced into the patient’s body. Chimeric antigen receptor (CAR) T-cell therapy is when a patient’s T cells are modified in a lab to better identify and attack cancer cells throughout the body. (CAR T cell therapy was the subject of a recent . You can also learn more about CAR T cell therapy and BiTEs from Dr. Edward Stadtmauer and Dr. Ajai Chari .)
Vaccines are another form of immunotherapy being studied in myeloma clinical trials. The goal of antitumor vaccination is to rev up or improve a patient’s immune response—that is, to enhance the immune system’s natural anti-cancer activity. In contrast to vaccines used for infectious diseases (for example the flu or pneumonia), which are preventive, cancer vaccines are typically therapeutic (intended to treat). In multiple myeloma, vaccines are generally considered to have the greatest potential when used in combination with other effective immunotherapies. (To learn more about myeloma vaccines, you can listen to Dr. David Avigan .)
The addition of antibody-based immunotherapies to the myeloma treatment arsenal and the emerging data on the immunotherapies still under study (cell-based therapies and vaccines) are highly promising advances in myeloma care. As studies progress, the best use of immunotherapies (for example, which patients are most likely to benefit) will come into clearer focus.
If you have more questions about immunotherapy, or want to know if a specific immunotherapy trial is available near you, Patient Navigators in the MMRF Patient Navigation Center are always available at 1-888-841-MMRF(6673).
Additional Resources
MMRF Immunotherapy Initiative: Chimeric Antigen Receptor (CAR) T-Cell Therapy.
ASH 2018 – Darzalex/Empliciti update.
ASH 2018 Day 3 – Immunotherapy.
MMRF Strategic Plan 2019. Immunotherapy.
Clinical Advances in Immunotherapy in Myeloma. Webinar 2: Vaccines for Myeloma (and Other Advances in Immunotherapy).
