Drug Combination Beneficial for Smoldering Multiple Myeloma

After several unsuccessful trials, researchers have identified a drug combination that hinders the progression of smoldering, or asymptomatic, multiple myeloma into full-fledged disease.

“We are very excited to see the first proof that early treatment is beneficial,” says Irene Ghobrial, MD, of Dana-Farber Cancer Institute in Boston, MA, who isn't connected to the study.

Smoldering multiple myeloma, a plasma-cell proliferative disorder, may cause no outward symptoms and typically is slow to flare into active illness. In the first 5 years after diagnosis, the risk of progressing is about 10% per year, she says.

However, for some high-risk patients, the chance of progression during the first 2 years can be around 50%, Ghobrial notes. These individuals show characteristics, such as substantial plasma cell intrusion into the bone marrow and high levels of monoclonal antibodies spawned by the aberrant plasma cells, that are the hallmark of this cancer.

Previously, efforts to halt progression with thalidomide, zoledronic acid, and the duo of melphalan and prednisone have not been effective, Ghobrial says. As a result, doctors usually observe rather than treat the disease.

In a study published in August in the New England Journal of Medicine, a team led by Jesus San Miguel, MD, of the Hospital Clinico Universitario de Salamanca in Spain, tested a combination of the thalidomide derivative lenalidomide (Revlimid; Celgene) and the corticosteroid dexamethasone. The drugs have been used individually and in combination to treat full-fledged multiple myeloma.

The researchers identified 119 patients with high-risk smoldering multiple myeloma and divided them into two groups. Half of the patients received lenalidomide and dexamethasone for 9 months, followed by lenalidomide alone for an additional 15 months. The other group of patients received no therapy unless they developed symptoms.

Three years after the start of the study, 94% of the treated patients were still alive, compared with 80% of the observation group, the team reported. In addition, just 23% of those treated experienced disease progression, versus 70% of the people in the observation-only group.

“I think this study is very significant for our patient population,” says Ghobrial. “It is the first to see improved progression-free survival and overall survival.” Studies are now evaluating whether other treatments, such as lenalidomide alone or the IL-6 inhibitor siltuximab, can also delay progression in high-risk patients with smoldering multiple myeloma.