Results from an ongoing Phase 2 clinical trial suggest that pomalidomide (Pomalyst) in combination with dexamethasone (Decadron) is effective and well-tolerated in patients who are resistant (refractory) to previous myeloma treatment with both Revlimid (lenalidomide) and Velcade (bortezomib). The findings were presented by Dr. Martha Lacy of the Mayo Clinic at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago on Saturday.

“We found the pomalidomide-dexamethasone regimen has significant activity in Revlimid- and Velcade-refractory myeloma,” said Dr. Lacy.

Pomalidomide is a new therapy being developed by Celgene and studied for the treatment of patients with relapsed or refractory myeloma. Similar to thalidomide (Thalomid) and Revlimid, pomalidomide works by stimulating the patient’s immune system to attack and destroy myeloma cells. In addition to its effects on the immune system, pomalidomide also inhibits the growth of new blood vessels, which stunts tumor growth by preventing nutrients and oxygen from reaching cancerous cells.

In previous clinical trials, combination therapy of pomalidomide and dexamethasone, abbreviated pom/dex, has resulted in overall response rates of 63 percent in patients with relapsed multiple myeloma and 32 percent in Revlimid-refractory patients.

The goal of this Phase 2 study was to determine the response rate and duration of remission in response to pom/dex treatment in patients refractory to both Revlimid and Velcade. Researchers also wanted to test the safety of the pom/dex regimen in this population of patients.

A total of 35 patients were enrolled in the trial, 81 percent of whom had received at least five prior treatment regimens. Forty three percent of the patients were considered high risk patients due to chromosomal abnormalities.

The participants were given pomalidomide every day during a 28-day cycle and received dexamethasone once a week (days 1, 8, 15, and 22 of the cycle). All patients also received aspirin daily to prevent the risk of blood clot formation. If patients experienced no response to therapy or experienced disease progression after two cycles of the pom/dex regimen, the daily dose of pomalidomide was doubled.

After treatment with pom/dex, the overall response rate was 26 percent, and an additional 28 percent of patients achieved a minor response. Typically, high-risk patients do not respond as well as low-risk patients. However, there was no significant difference in the response rates for the overall study group and the high-risk patients.

Of the nine patients that increased the dosage of pomalidomide after two cycles, all but one, who experienced a minor response, remained in a stable disease state following the pom/dex treatment.

“We found that this regimen acted rapidly,” said Dr. Lacy. The average time until patients responded to the pom/dex treatment was one month.

Dr. Bart Barlogie of the University of Arkansas responded, “The median time [to response] of one month is very rapid. If it’s so rapid, this would be the best treatment to be given upfront.”

At the time of analysis, 51 percent of the patients remained on trial, with the major reason for going off the study being disease progression. Follow-up showed that 86 percent of patients were alive and 58 percent of patients remained progression free six months after pom/dex treatment.

“Toxicity was manageable and consisted primarily of [low white blood cell counts],” said Dr. Lacy.

The most common serious side effects were low levels of white blood cells (34 percent of patients), platelets (9 percent), and red blood cells (9 percent) as well as nerve damage to extremities (14 percent). Other serious side effects were uncommon.

Based on the results of this Phase 2 study, Dr. Lacy and her colleagues concluded that pom/dex was well-tolerated in heavily pre-treated Revlimid- and Velcade-refractory multiple myeloma patients. They also noted that pom/dex treatment resulted in a rapid response and good rates of remission, confirming the therapeutic benefit for pom/dex in this patient population.

“Very impressive data,” said Dr. Sagar Lonial of Emory Winship Cancer Institute in a discussion session following Dr. Lacy’s presentation. “These were probably some of the most heavily pre-treated patients that we have ever seen in clinical trials.”

Ongoing studies will determine if beginning treatment with the higher dose of pomalidomide will improve the overall response rate.

For more information, please see abstract 8002 on the ASCO meeting website.