Results of a small Phase 2 study show that newly diagnosed multiple myeloma patients achieve similar response rates with alternating weeks of Revlimid and thalidomide in combination with dexamethasone as patients receiving Revlimid with dexamethasone or thalidomide with dexamethasone.

The study investigators point out that the alternating regimen was well tolerated even though Revlimid was administered at a higher than usual dose of 50 mg per day. However, the regimen was not, as they had hoped, more effective than either Revlimid ^[1] (lenalidomide) or thalidomide ^[2] (Thalomid) alone in combination with dexamethasone ^[3] (Decadron).

They therefore conclude that Revlimid with low-dose dexamethasone remains one of the standards of care for newly diagnosed multiple myeloma patients.

“It is unlikely that this regimen will be utilized to treat myeloma patients. However, the study does show that Revlimid may be administered safely at higher doses,” said Dr. Madiha Tufail, the study’s lead investigator from the John Theurer Cancer Center in Hackensack, New Jersey.

Dr. Tufail suggests alternative dosing schedules may lead to more promising results.

“This pilot trial may lead to a trial of more intense Revlimid therapy with 50 mg administered in the standard of 21 successive days (instead of every other week), which may result in higher response rates. In addition, it may be of interest to administer thalidomide and Revlimid concurrently instead of the alternating week schedule to see if high response rates may be achieved,” she explained.

Revlimid and thalidomide belong to a class of drugs called immunomodulatory agents. Even though they belong to the same class of drugs, they are associated with different side effects. Thalidomide leads to high rates of peripheral neuropathy (pain or tingling in the extremities due to nerve damage), while the most common side effect of Revlimid is low blood cell counts (see related Beacon ^[4] news).

In this Phase 2 trial, Dr. Tufail and her colleagues alternated the weeks in which they administered Revlimid and thalidomide. They hypothesized that this schedule would reduce side effects associated with each drug, which in turn would increase schedule adherence and decrease the need for dosage reductions. By maintaining effective doses of each drug, the researchers hoped to see an improvement in response rates without increasing the side effects.

Between November 2009 and January 2011, 22 newly diagnosed myeloma patients with a median age of 62 years were enrolled in the study. The patients received four 28-day cycles of induction therapy with Revlimid, thalidomide, and dexamethasone followed by an autologous stem cell transplant.

In each cycle of therapy, patients received 200 mg of thalidomide daily during the first and third week.  Revlimid was administered at 25 mg daily during the second and fourth week of the first cycle; if Revlimid was well tolerated during the first cycle, the dosage was increased to 50 mg in subsequent cycles. Additionally, the patients received 40 mg of dexamethasone once peer week throughout each treatment cycle.

Patients received a median of 3.5 cycles of therapy. Eighty-six percent of the patients received the escalated dosage of 50 mg Revlimid during the second cycle; however, 24 percent later reduced their dosage back to 25 mg due to low blood cell counts.

The overall response rate after the induction therapy was 68 percent, with 4 percent achieving a very good partial response and 64 percent a partial response. Additionally, 23 percent of patients achieved a minimal response.

According to the study investigators, the overall response rate is identical to that which has been observed with Revlimid plus dexamethasone or thalidomide plus dexamethasone alone after four months of treatment in similar patients.

Severe side effects included low white blood cell counts (14 percent), low red blood cell counts (14 percent), constipation (14 percent), and rash (9 percent). One early death occurred due to pneumonia. No severe rates of peripheral neuropathy or blood clotting were observed.

“The toxicity profile in our study was better than reported in the literature,” explained Dr. Tufail. “Clinically significant neuropathy was not observed - probably due to the alternating weekly schedule.  [Low blood cell counts] were minimal, even at double the standard dose of Revlimid.”

For more information, please see the study in Clinical Lymphoma Myeloma and Leukemia ^[5] (abstract).