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Immunotherapy for Multiple Myeloma

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  • Multiple Myeloma
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

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

Reviewed By: Hearn Jay Cho, M.D., Ph.D.
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Mount Sinai School of Medicine
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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 2018, there were approximately 31,000 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.

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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.

There are currently two FDA-approved immunotherapy options for multiple myeloma.

Targeted Antibodies

  • 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

Immunotherapy is a promising new treatment option for multiple myeloma patients, with the potential to result in long term cancer remission after allogeneic, donor 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, many myeloma patients are ineligible for this allogeneic transplantation due to restrictions related to age and medical conditions.

Many other immunotherapies are showing varying degrees of success against multiple myeloma in clinical trials, both for advanced cases as well as newly diagnosed and previously untreated patients.

Find a multiple myeloma clinical trial

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, Ph.D., 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, M.D. (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, M.D., Ph.D., 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.

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Featured Patient

There's no question in my mind that immunotherapy saved my life.

Mary Elizabeth Williams
Melanoma  |  Diagnosed 2010
Read My Story
Featured Scientist
Markus Muschen, M.D., Ph.D.
City of Hope National Medical Center
CLIP Investigator  |  2016
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CRI Immunotherapy Patient Summit in San Diego on June 29, 2019 

Multiple Myeloma Statistics

2nd Most common form of blood cancer
1 in 132 Men and women will develop myeloma in their lifetime
150k Newly diagnosed patients each year globally

Multiple Myeloma Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

Therapies
  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunomodulators
  • Oncolytic Virus Therapy

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in multiple myeloma clinical trials include:

  • BCMA: an important signaling receptor found mainly on mature B cells; often expressed by lymphoma and myeloma cells
  • CD19: a receptor found on the surface of almost all B immune cells that influences their growth, development, and activity; often expressed by leukemia, lymphoma, and myeloma cells
  • CD20: a receptor found on the surface of B immune cells during their development; often expressed by leukemia, lymphoma, and myeloma cells
  • CD38: an immune cell surface protein that plays roles in cell adhesion and signaling; often expressed by leukemia and myeloma cells
  • CD52: a protein found on the surface of mature immune cells as well as other cell types
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • SLAMF7: a surface protein found on plasma B cells; often expressed by lymphoma and myeloma cells

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in multiple myeloma clinical trials include:

  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in cancer cells, flagging them as abnormal to the immune system
  • Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
  • Telomerase: an enzyme that helps maintain the health of cellular DNA; exploited by cancer cells to achieve immortality
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in multiple myeloma clinical trials include:

  • BCMA: an important signaling receptor found mainly on mature B cells; often expressed by lymphoma and myeloma cells
  • CD19: a receptor found on the surface of almost all B cells that influences their growth, development, and activity; often expressed by leukemia, lymphoma, and myeloma cells
  • CD20: a receptor found on the surface of B cells during their development; often expressed by leukemia, lymphoma, and myeloma cells
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in multiple myeloma clinical trials include:

  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses modified viruses that can infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in multiple myeloma clinical trials include:

  • Measles virus: a highly contagious virus that infects the respiratory tract and can cause measles
  • Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
  • Vesicular stomatitis virus: a virus that belongs to the same family as the rabies virus; can cause flu-like symptoms in humans
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Sources: ACS Facts and Figures 2018; Altor Bioscience Corp.; ClinicalTrials.gov; CRI documents; GLOBOCAN 2018; Journal of the National Cancer Institute (PMID: 12953083); National Cancer Institute (NCI); New England Journal of Medicine (DOI: 10.1056/NEJMra041875)

Updated February 2019

*Immunotherapy results may vary from patient to patient. Consult a healthcare professional about your treatment options.

*Immunotherapy results may vary from patient to patient.

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