Immunotherapy
For Multiple Myeloma

How is Immunotherapy for Multiple Myeloma Changing the Outlook for Patients?

Reviewed by:

Hearn Jay Cho, MD, PhD
Multiple Myeloma Center of Excellence, Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai

Immunotherapy for multiple myeloma is a promising new treatment option, with the potential to result in long-term cancer remission similar to the results of allogeneic bone marrow transplantation with less risk for complications.

Myeloma—also referred to as multiple myeloma or plasma cell myeloma—is a cancer that originates in plasma cells, a type of white blood cell found in the bone marrow that makes antibodies. When a plasma cell becomes cancerous, it is referred to as myeloma. Myeloma cells grow in an out-of-control manner and accumulate in bone marrow. Over time, the tumor cells may directly damage the bones, causing fractures and dangerously elevated blood calcium levels, and may damage the kidneys. Myeloma cells interfere with blood production, which can result in anemia (a shortage of red blood cells). Myeloma cells also suppress normal white blood cell production, interfering with normal immunity and leaving the patients vulnerable to infections.

Globally, there are an estimated 160,000 new cases of multiple myeloma diagnosed each year, along with 110,000 deaths due to the disease. Multiple myeloma is the second-most common form of blood cancer in the United States, comprising about 1% of all cancers. In 2023, there will be an estimated 36,000 new cases of myeloma, and about 13,000 deaths caused by the disease. In the U.S., it is estimated that 1 in 132 men and women will develop myeloma at some point in their lifetimes.

Multiple Myeloma Treatment Options

Multiple myeloma is diagnosed when elevated abnormal plasma cells in the bone marrow are detected, and a treatment regimen is structured around the symptoms of organ damage from the cancer. Current treatment protocols for symptomatic myeloma involve chemotherapy, autologous stem cell transplantation, and in some instances, radiation therapy.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently five FDA-approved immunotherapy options for multiple myeloma.

Adoptive Cell Therapy

• Ciltacabtagene autoleucel (Carvykti™): a BCMA-targeting CAR T cell immunotherapy; approved for subsets of patients with advanced multiple myeloma
• Idecabtagene vicleucel (Abecma™): a BCMA-targeting CAR T cell immunotherapy; approved for subsets of patients with advanced multiple myeloma 

Targeted Antibodies

Immunotherapy is a promising new treatment option for multiple myeloma patients, with the potential to result in long term cancer remission similar to the results of allogeneic bone marrow transplantation of blood stem cells. The new immune system generated from the stem cell transplant process is able to recognize and kill myeloma cells in the “graft-vs-myeloma” effect, showing that the body’s immune system does have the potential to eliminate multiple myeloma cells. However, there are significant risks for illness or death due to complications related to the transplant, and the majority of myeloma patients are ineligible for this allogeneic transplantation due to restrictions related to age and medical conditions. Therefore, there is a critical need for immunotherapies that have similar outcomes as allogeneic transplantation with reduced risks.

• Daratumumab (Darzalex®): a monoclonal antibody that targets the CD38 pathway; approved for subsets of patients with advanced multiple myeloma
• Elotuzumab (Empliciti®): a monoclonal antibody that targets the SLAMF7 pathway; approved for subsets of patients with advanced multiple myeloma
• Isatuximab (Sarclisa®): a monoclonal antibody that targets the CD38 pathway; approved for subsets of patients with advanced multiple myeloma
• Teclistimab (Tecvayli^TM): a bispecific T cell engager (BiTE) antibody that targets BCMA on tumor cells as well as CD3 on T cells; approved for subsets of patients with multiple myeloma
  

In addition to the FDA-approved therapies listed above, there are several new classes of myeloma immunotherapy in clinical trials. These include second generation monoclonal antibodies targeting CD38 and other targets, chimeric antigen receptor (CAR) T cells, antibody-drug conjugates (ADC), and bi-specific T cell and Natural Killer cell engaging agents. Some of these agents are in pivotal clinical trials now and are expected to receive conditional or full approval in the near future. Patients may consult with their physicians to explore clinical trials that may be appropriate.

CRI’s Impact in Multiple Myeloma

Through our ongoing grant and fellowship programs, clinical studies, and multiple myeloma initiatives, we provide funding for research that seeks to further understand and more effectively treat multiple myeloma. Current studies are being conducted into non-invasive measurements of myeloma tumor progression, disease regression in patients treated for recurrent multiple myeloma and the utilization of myeloma-specific T cells in treatment, and combination immunotherapy targeting myeloma-associated MAGE antigens.

• CRI postdoctoral fellow Diego Acosta-Alvear, PhD, at the University of California, San Francisco, is studying how a mechanism called the unfolded protein response contributes to multiple myeloma progression.
• At Memorial Sloan Kettering Cancer Center, CRI predoctoral fellow Eleanor Tyler studied the involvement of T cell responses specific to the myeloma antigens CT7/MAGE-C1 and WT1 in disease regression following stem cell transplantation.
• Djordje Atanackovic, MD (CRI Investigator, 2007-2011), and colleagues at the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany, identified the cell receptor CD229 as the most strongly over-expressed antigen in multiple myeloma, suggesting that it could be a promising target for anti-myeloma therapies.
• Hearn Jay Cho, MD, PhD, at Mount Sinai School of Medicine, discovered that two of the type I Melanoma Antigen Genes (MAGE), MAGE-A3 and CT7/MAGE-C1, are expressed in the tumors of more than 75 percent of myeloma patients, and demonstrated that MAGE-A3 is a critical survival factor in multiple myeloma that makes these cells resistant to normal cell death and killing by chemotherapy agents, providing further evidence that MAGE proteins may be excellent candidates for tumor vaccines targeting multiple myeloma.

See what multiple myeloma cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way cancer is treated—saving more lives.