Multiple Myeloma

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Smoldering Myeloma — Keeping it from Becoming Active

Dr. Irene Ghobrial Dana-Farber Cancer Institute

Smoldering myeloma is a disease that often comes before development of full blown myeloma. In other words, it’s very close to becoming active myeloma, but does not have any symptoms. It is characterized by higher levels of abnormal proteins in the blood and plasma cells that make up greater than 10% of the bone marrow. So the goal with smoldering myeloma is to keep it from becoming active disease.

The chance of progressing to malignant myeloma differs based on the riskiness of the smoldering myeloma. Patients with smoldering myeloma typically have a 10% lifetime chance of progressing to active multiple myeloma, but patients with high risk smoldering myeloma have a 50% chance of progressing to active multiple myeloma within just two years following diagnosis.

The current approach to treating smoldering myeloma is to “watch and wait.” However, Dr. Irene Ghobrial medical oncologist at the Dana Farber Cancer Institute says waiting  too long can produce active myeloma and serious symptoms. The changes in the blood and bone can eventually become worse, and end up affecting different parts of the body, producing symptoms like bone fractures and organ damage. Once these injuries occur, patients are started on a three-phase myeloma treatment, which includes steroids, immune system-activating drugs, chemotherapy, and stem-cell transplantation.

Dr. Ghobrial believes this approach doesn’t really make sense. “You can think of it in…breast cancer for example. A woman would have early breast lesions–we would never tell her, ‘wait until you have metastatic lesions everywhere. Wait until you’re fracturing your bones and then I’ll treat you.’ We do that in myeloma every day. We tell them, ‘wait, you have smoldering myeloma. You don’t have symptoms. So, wait until you have lesions and fractures and then I’ll treat you.’

Researchers like Dr. Ghobrial, however, are working to develop treatments for smoldering myeloma keeping it from becoming active disease. She wants to  cure patients of the disease before they develop serious symptoms or active myeloma. “We want to change [the current approach].” That’s why Dr. Ghobrial uses treatments typically reserved for the first phase of active myeloma in patients with smoldering. “You can have a better survival with lenalidomide and [dexamethasone].” Those two drugs are part of first-line therapy for active multiple myeloma now being used against smoldering . Lenalidomide is a drug that prevents myeloma cells from processing proteins key to survival, while also activating the immune system. Dexamethasone is a steroid drug that can help reduce inflammation and pain while also killing myeloma cells when given in high doses.

Ghobrial says there is evidence that another drug may be very effective against smoldering myeloma, “We added an antibody that activates the immune system, something called elotuzumab.” Elotuzumab is an antibody, a protein, that binds to a receptor expressed on myeloma cells.  By “tagging” myeloma cells with this protein, the drug makes the cells easily visible to immune cells that can target and kill them. Ghobrial says the results have been dramatic.

“After three years of follow-up, we have not seen anyone develop active myeloma when they were on (Elotuzumab). So, it’s an exciting time for us. We think that by doing that, as well as other combinations of therapy that we have, we could potentially prevent progression in our patients with myeloma.”

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Dr. Irene Ghobrial is a Medical Oncologist at Dana-Farber Cancer Institute. Read More