The most recent results of a Spanish Phase 3 clinical trial indicate that Revlimid in combination with dexamethasone delays disease progression in smoldering multiple myeloma patients who have a high risk of developing symptomatic disease.

Specifically, the results showed that high-risk smoldering multiple myeloma patients who received Revlimid plus dexamethasone had a longer time to disease progression and better overall survival than patients who did not receive treatment.

However, the Spanish researchers acknowledged that these results should be confirmed by long-term follow-up data, especially regarding the difference in overall survival.

Dr. Ola Landgren of the U.S. National Institutes of Health, who has done extensive research on smoldering myeloma, described the results of the Spanish study as "very important."

"This is the first treatment study of high-risk smoldering multiple myeloma showing that treatment is associated with improved overall survival,” he added.  “In my opinion, it has the potential to influence and change the way high-risk smoldering myeloma patients are being managed in the clinic. It could potentially lead to more advanced therapies for high-risk smoldering myeloma, and maybe some patients will be cured while others will have a significant delay in the progression of the disease.”

Dr. María-Victoria Mateos from the Hospital Clinico Universitario in Salamanca, Spain, presented the updated Phase 3 results at the American Society for Hematology (ASH) annual meeting in San Diego last month.

Dr. Mateos discussed initial results of this trial during a debate with Dr. Sagar Lonial of Emory University at the International Myeloma Workshop earlier this year (see related Beacon news and detailed coverage of the debate in the Beacon’s discussion forum).

Smoldering, or asymptomatic, multiple myeloma is a blood disorder characterized by an excess of monoclonal protein in the blood and urine. A diagnosis of smoldering multiple myeloma is given when a patient’s monoclonal protein level is at least 30 g/L or the proportion of plasma cells in the bone marrow is at least 10 percent, but the patient experiences none of the symptoms typically associated with multiple myeloma (elevated calcium levels, kidney failure, anemia, or bone lesions). Patients with smoldering multiple myeloma generally receive no treatment until their disease progresses.

Certain factors have been shown to increase the risk of progression to symptomatic disease in patients with smoldering multiple myeloma. These include a monoclonal protein level exceeding 30 g/L, plasma cells exceeding 10 percent in the bone marrow, abnormal plasma cells exceeding 95 percent, or the presence of small parts of antibodies (as indicated by an abnormal free light chain ratio).

Several past clinical trials have investigated the effects of melphalan (Alkeran) plus prednisone, thalidomide (Thalomid), and bisphosphonates in patients with smoldering multiple myeloma. According to the study authors, however, these clinical trials did not distinguish between standard-risk and high-risk smoldering multiple myeloma patients. The authors explained that standard-risk patients would probably not benefit from treatment, whereas high-risk patients may benefit from early treatment to delay the progression of the disease.

In this Phase 3 clinical trial, researchers investigated whether treatment with Revlimid (lenalidomide) plus dexa­methasone (Decadron) would prolong the time to progression to symptomatic disease in high-risk smoldering multiple myeloma patients.

A total of 119 patients were randomly assigned to either the treatment arm (57 patients) or the non-treatment arm (62 patients). The patients had a median age of 61 years and 65 years, respectively.

Patients in the treatment arm received an initial therapy consisting of nine four-week cycles of Revlimid plus dexamethasone. During each cycle, they received 25 mg of Revlimid daily on days 1 to 21 and 20 mg of dexamethasone daily on days 1 to 4 and 12 to 15. They then received maintenance therapy consisting of 10 mg of Revlimid on days 1 to 21 every month until disease progression or two years of treatment.

Patients in the non-treatment arm did not receive any form of treatment during the study.

Of the 57 patients in the Revlimid-dexamethasone treatment group, 86 percent achieved a partial response or better, including 14 percent of patients who achieved a complete response.

Fifty of the 57 patients went on to receive Revlimid maintenance therapy. The complete response rate increased to 25 percent after a median of 15 cycles of maintenance therapy.

After a median follow-up of 32 months, 15 percent of patients who received the Revlimid-dexamethasone therapy progressed to symptomatic disease, compared to 59 percent of patients who did not receive treatment.

The median time to disease progression was 23 months for patients in the non-treatment arm; the median has not yet been reached for patients treated with Revlimid-dexamethasone.

The estimated three-year overall survival rate is 93 percent for patients who received Revlimid-dexamethasone and 76 percent for patients who did not.

The most common side effects for patients in the treatment arm during initial therapy were mild to moderate infections (46 percent), rash (33 percent), low red blood cell counts (28 percent), and diarrhea (24 percent). Severe side effects included loss of strength (7 percent), infections (6 percent), and low white blood cell counts (5 percent).

For more information, see abstract 303 on the ASH meeting website. The Myeloma Beacon will also publish later this week an interview with Dr. Landgren about the results of the study by Dr. Mateos and her colleagues and the implications of those results for the treatment of smoldering myeloma.