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Second Cancers and Myeloma: Understanding the Connection

Posted on May 04, 2022
Medically reviewed by
Todd Gersten, M.D.
Article written by
Aminah Wali, Ph.D.

For people undergoing treatment for multiple myeloma, eliminating the primary cancer is the main concern — but there is also a risk of developing a secondary cancer later in life. Second cancers may develop years after receiving cancer treatment. They are generally a long-term side effect of the cancer treatment itself.

Common Types of Second Cancers

Secondary cancers can be solid tumors, but they are more often blood cancers (also called hematologic malignancies). People who have been treated for multiple myeloma have an increased risk of developing two types of blood cancers: acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Acute Myeloid Leukemia

AML is a fast-growing cancer that forms from white blood cells. It initially forms in the bone marrow, but it can spread to other parts of the body.

Myelodysplastic Syndrome

MDS is a slower-growing disease that also forms in blood cells of the bone marrow. In some cases, MDS can eventually progress and turn into AML.

Who Gets Second Cancers?

Secondary cancers are more likely to develop in people diagnosed with multiple myeloma before age 70. Antibodies — proteins that help the immune system fight infection — may also play a role. People with certain antibodies may have a higher risk of developing MDS and AML.

Other individual risk factors that increase the likelihood of developing secondary cancers are not well understood. However, researchers are investigating genetic and behavioral factors.

What Causes Second Cancers After Multiple Myeloma?

Certain treatments for multiple myeloma have been linked to an increased risk for developing MDS and AML. There are also biological factors that may come into play.

Melphalan

Melphalan (Alkeran) is a chemotherapy drug used in the treatment of multiple myeloma. Melphalan may be given during a chemotherapy course or paired with an autologous stem cell transplant.

Research has shown that treatment with melphalan increases the risk of AML and MDS, particularly when taking the drug for a long time. The proportion of people who develop AML or MDS after taking melphalan varies between studies, but the overall risk of developing a second cancer is around 5 percent.

Lenalidomide

Lenalidomide (Revlimid) was approved by the U.S. Food and Drug Administration (FDA) in 2015 for treating multiple myeloma. Lenalidomide is an immunomodulatory drug. It boosts a person’s immune system so it better recognizes and attacks cancer cells.

Although lenalidomide is effective against cancer, clinical trials have shown a potential risk of secondary cancers following treatment. People treated with lenalidomide can be more than twice as likely to develop a second cancer than those who did not receive treatment.

In spite of this relative risk, the overall chance of developing a second cancer as a result of lenalidomide treatment is still low, with incidence rates ranging from 1.5 percent to 7.4 percent.

Radiation Therapy

Radiation therapy is a common treatment option for multiple myeloma, especially in cases where the cancer is located in one location rather than throughout the body. Using radiation to treat other diseases like breast cancer has been shown to increase the risk of secondary cancers. However, researchers are still investigating whether treating multiple myeloma with radiation can increase the risk of secondary cancers.

Biological Factors

Multiple myeloma forms from a type of white blood cell called a plasma cell. Plasma cells can have genetic abnormalities that result in myeloma cells. These changes can also result in high levels of a protein called M protein, often referred to as myeloma protein.

In people with an early form of multiple myeloma called monoclonal gammopathy of undetermined significance (MGUS), high levels of M protein are associated with a higher risk for AML and MDS. People with MGUS who have high levels of the antibodies immunoglobulin A and immunoglobulin G may also be up to 8 times as likely to develop AML or MDS.

Managing Risk of Second Cancers After Multiple Myeloma

Unfortunately, it’s difficult to predict the likelihood of getting a second cancer following myeloma treatment. However, there are steps you can take to reduce your risk of getting another cancer.

  • People undergoing cancer treatment are encouraged to maintain a healthy lifestyle with physical activity and good nutrition.
  • It’s important to maintain regular follow-up visits with your health care provider to detect any second cancers and begin treatment as soon as possible.
  • Additionally, it’s crucial to continue research and participation in clinical trials. These trials can identify multiple myeloma treatments that are effective at treating cancer with a lower risk of causing long-term side effects.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people with multiple myeloma and their loved ones. On MyMyelomaTeam, more than 15,000 members come together to ask questions, give advice, and share their stories with others who understand life with myeloma.

Are you living with a second cancer after multiple myeloma? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here.

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