Multiple Myeloma: Chemotherapy, Immune-Modifying Drugs & Proteasome Inhibitors

While the ultimate goal remains curing multiple myeloma, current drugs cannot completely eliminate the disease. However, these drugs can be used to control multiple myeloma, similar to the way insulin is used to control diabetes.

Our doctors use several classes of drugs to treat multiple myeloma, including chemotherapies, immune-modulating drugs (IMiDs), and proteasome inhibitors. These drugs can be used in various combinations that include two, three, or even four drugs to achieve the best outcomes.

Increasing the number of drugs in combination can improve their effectiveness, but they also increase side effects such as nausea, fatigue, rashes, or more serious conditions such as shortness of breath and seizures. A great deal of research is ongoing at Memorial Sloan Kettering to try to determine the best drug combinations and how to use them most effectively.

You may be treated with medications alone if the drugs show enough benefit in controlling the disease. In other circumstances, your physician may recommend high doses of chemotherapy followed by stem cell transplantation, which replaces the bone marrow cells that chemotherapy destroys.

Chemotherapy

Chemotherapy is a drug or combination of drugs that spreads throughout the body to kill cancer cells and control their growth. You can receive chemotherapy by mouth or through an IV.

Memorial Sloan Kettering’s multiple myeloma disease management team includes medical oncologists who specialize in planning your chemotherapy for the disease. Our physicians understand the subtleties of chemotherapy regimens and will personalize your treatment, optimizing its strength while minimizing side effects.

The most common chemotherapy treatment for multiple myeloma includes the drug dexamethasone, given either alone or in combination with other chemotherapy drugs such as melphalan, doxorubicin, and cyclophosphamide, or with other types of medications described below.

Immune-Modifying Drugs

Immune-modifying drugs can be used to help the immune system fight the cancerous plasma cells or keep them from multiplying. Our doctors use one of three immune-modifying drugs to treat multiple myeloma — thalidomide, lenalidomide, or pomalidomide. These drugs are taken in capsule form and are usually combined with another drug, such as dexamethasone.

Thalidomide, a medicine first used in the late 1950s as a sedative and to combat nausea during pregnancy, was banned for decades after it was found to cause birth defects. In the late 1990s, however, cancer researchers discovered that thalidomide is an effective treatment for myeloma, both in newly diagnosed patients and as a maintenance treatment in patients whose disease has been brought under control, to keep it from returning. Thalidomide is also given to multiple myeloma patients if the disease returns, or relapses.

Lenalidomide (Revlimid®) is a newer form of thalidomide designed to be more potent and have fewer side effects than thalidomide, although both can cause tingling or numbness, fatigue, rashes, and more serious conditions such as shortness of breath or seizures.

Pomalidomide (Pomalyst®) is the most recent immune-modifying drug approved by the US Food and Drug Administration for patients with multiple myeloma. It is similar to lenalidomide, but it can be effective when lenalidomide and other drugs stop working.

Researchers believe thalidomide, lenalidomide, and pomalidomide enhance the body’s immune response to promote the death of cancer cells and to prevent myeloma cell growth and survival in bone marrow. Our doctors use a combination of lenalidomide and low-dose dexamethasone (chemotherapy) to treat many newly diagnosed patients who have limited organ damage.

Proteasome Inhibitors

In 2003, the FDA approved bortezomib (Velcade®), a new type of drug called a proteasome inhibitor, for multiple myeloma. Bortezomib blocks the activity of the proteasome, a complex of enzymes found in cells that normally regulates the removal of defective proteins. Inhibiting proteasome function leads to the accumulation of defective proteins, which can trigger cell death. Cancerous cells such as myeloma cells seem to be more sensitive than normal cells to this effect, although some healthy cells can be harmed.

Bortezomib was the first proteasome inhibitor approved to treat patients who had already been treated with two other types of chemotherapy and whose cancer has still progressed after the most recent therapy. Then, in 2008, partly as a result of clinical trials led by Memorial Sloan Kettering investigators, bortezomib was approved for use against multiple myeloma in the initial phase of treatment, as it was shown to be very effective in these cases.

Carfilzomib (Kyprolis®) is a newer proteasome inhibitor available to multiple myeloma patients for whom bortezomib and other treatments have proven ineffective, or whose multiple myeloma has returned after an earlier treatment. Carfilzomib has different side effects from bortezomib and also can be effective when bortezomib and other drugs stop working.

Investigative Approaches

Memorial Sloan Kettering researchers are developing new agents for cancer treatment at a faster rate than at any time since chemotherapeutic drugs were introduced in the late 1940s. Relying in part on information that is emerging about the genetic basis of multiple myeloma, our investigators are pursuing a variety of strategies to find better drugs to control the disease.

Through clinical trials, our investigators are assessing the optimal timing and combinations of traditional chemotherapy drugs with immune-modifying drugs, such as lenalidomide and pomalidomide, and proteasome inhibitors such as bortezomib. Our researchers also continue to investigate newer proteasome inhibitors, such as MLN9708, and new approaches, such as using higher doses of carfilzomib.