A recent study published in the journal Blood suggests that treatment of newly diagnosed multiple myeloma with Revlimid ^[1] (lenalidomide) plus dexamethasone ^[2](Decadron) may be more effective and better tolerated than the approved thalidomide ^[1] (Thalomid) plus dexamethasone regimen commonly used in newly diagnosed patients.

Both Revlimid and thalidomide are considered immunomodulatory agents. This means that they work by having an affect on the immune system. Specifically, these drugs are believed to encourage a patient’s immune system to attack and destroy myeloma cells.

Thalidomide was originally developed in the 1950s, however it was not until 1999 that it was found to be highly effective against multiple myeloma. It is currently approved by the United States Food and Drug Administration in combination with the corticosteroid dexamethasone for treatment in newly diagnosed multiple myeloma patients.

Revlimid, a molecular derivative of thalidomide, was first introduced in 2004. It was designed to be more potent and have fewer side effects than its parent drug. Currently, it is approved for use in combination with dexamethasone for treatment of patients with multiple myeloma who have had at least one prior therapy. Preliminary results ^[3] from an ongoing Phase 3 clinical trial of newly diagnosed myeloma patients also indicate efficacy as a first line treatment.

In the current study, investigators conducted a retrospective analysis of 411 patients newly diagnosed with multiple myeloma. The participants were treated with either Revlimid/dexamethasone (228 patients) or thalidomide/dexamethasone (183 patients). This study marks the first formal comparison of the two combination therapies.

Response rates were higher for the Revlimid/dexamethasone group compared to the thalidomide/dexamethasone group, with 80 percent and 61 percent of patients, respectively, achieving at least a partial response. Complete plus very good partial responses also favored Revlimid/dexamethasone treatment (34 percent for the Revlimid regimen versus 12 percent for the thalidomide regimen). Results were reported according to uniform response criteria ^[4] established by the International Myeloma Working Group.

In addition, patients treated with Revlimid/dexamethasone experienced longer time-to-progression, progression-free survival, and overall survival. Median overall survival was 57 months for patients using thalidomide/dexamethasone and significantly longer for patients on Revlimid/dexamethasone. The survival time for the Revlimid patients was not yet able to be determined.

"The study shows that if Revlimid is available, it is clearly the superior immunomodulatory drug compared with thalidomide for treatment of multiple myeloma,” wrote Dr. S. Vincent Rajkumar, physician and professor of medicine at the Mayo Clinic, in an e-mail to The Myeloma Beacon.

Side effects differed between the two treatment groups. The most common side effect in patients treated with thalidomide/dexamethasone was peripheral neuropathy (pain and numbness in the hands and feet), which was reported in 15 percent of patients and was the main reason for discontinuation of thalidomide. The most common side effects in patients treated with Revlimid/dexamethasone were blood-related. Specifically, 14 percent of patients experienced neutropenia, a blood disorder characterized by abnormally low neutrophils, an important type of white blood cell that fights infection.

Dr. Rajkumar, who is also one of the investigators of the study, said, “Revlimid and low dose dexamethasone is one of the best frontline treatments today for newly diagnosed myeloma taking into account its efficacy as well as the quality of life. There are data that show more aggressive treatments can give better complete response rates than Revlimid/dexamethasone, but the overall survival results with Revlimid and low dose dexamethasone with or without stem cell transplantation are as good as any regimen out there.”

The investigators of the study point out that randomized trials are still needed to confirm these results and compare them to other common treatment regimens in order to determine the optimal initial therapy for multiple myeloma patients.

For more information, please see the study in Blood ^[5] (abstract).