Pomalidomide in combination with low-dose dexamethasone demonstrates a significant progression free survival and overall survival advantage, in relapsed/refractory multiple myeloma: Phase III, multicenter, randomized, open-label study

An advanced trial comparing therapeutic options for refractory multiple myeloma finds that combination treatment with pomalidomide and low-dose dexamethasone may be superior to high-dose dexamethasone alone for patients with resistant and relapsed disease.

Multiple myeloma (MM) causes abnormal plasma cells to accumulate in the bone marrow, interfering with normal blood cell production and increasing the risk of infection and abnormal bleeding.

Current treatments include combinations of steroid therapies like dexamethasone, which reduces inflammation and manages the immune response with targeted therapies like bortezomib and lenalidomide that inhibit tumor growth and reproduction.

However, many patients eventually become resistant to these standard therapies and therefore have a poor prognosis.

Since there are few treatment options available for these difficult-to-treat patients, research has aimed to identify new therapy combinations and disease targets that may lead to better results.

Early trials of a novel immunomodulatory drug called pomalidomide have shown some evidence of activity in these relapsed and treatment-resistant patients.

Pomalidomide offers an effective mechanism against resistant myeloma because it directly targets the disease in multiple ways.

It not only encourages the immune system to attack and destroy myeloma cells, but also prevents the growth of new blood vessels and inhibits myeloma cell growth by reducing the supply of oxygen and nutrients to the myeloma cells.

To evaluate whether a combination regimen with pomalidomide plus low-dose dexamethasone therapy might offer relapsed multiple myeloma patients better progression-free and overall survival than high-dose dexamethasone alone, researchers conducted a study in a population of patients with refractory or relapsed and refractory disease.

The open-label, multicenter, Phase III trial evaluated the safety and efficacy of pomalidomide and low-dose dexamethasone (LoDEX) combination as compared to high-dose dexamethasone (HiDEX) alone. A total of 455 patients were enrolled and randomized to receive regimens of either pomalidomide with LoDEX (Arm A, 302 patients) or HiDEX (Arm B, 153 patients) in a 28-day cycle until disease progression or severe toxicity.

The primary endpoint was progression-free survival (PFS), while secondary endpoints included measures of safety, overall survival, and quality of life.

After a median follow-up of 18 weeks, patients who received the pomalidomide and LoDEX combination experienced significantly longer PFS compared with those who received HiDEX alone (15.7 vs. 8 weeks), and overall survival was also longer in the combination treatment arm. After an independent review committee concluded that the combination regimen offered survival advantage, the study’s Data Safety Monitoring Board recommended that patients from Arm B be switched to Arm A to receive the combination treatment.

The combination regimen was well tolerated among the study participants, although some expected toxicities were reported in both groups, including low neutrophil count (42% in Arm A vs. 15% in Arm B), low platelet count (21% vs. 24%), and fever (7% vs. 0%).

At the time of analysis, 45 percent of patients in Arm A and 25 percent of patients in Arm B remained in the study. The primary reason cited for discontinuation was progressive disease, which occurred in 35 percent of patients in Arm A and 49 percent in Arm B. One-fourth (25%) of patients in Arm A and 38 percent in Arm B died during the study, primarily from advanced disease and infections.

“We are excited about these results, as they show that a combination approach with pomalidomide and low-dose dexamethasone offers superior results than current treatment options for hard-to-treat myeloma patients,” said Meletios Dimopoulos, MD, lead author and Professor and Chairman of the Department of Clinical Therapeutics at Alexandra Hospital in Athens, Greece. “We believe this study provides the basis to consider this combination as a new standard of care for patients who have exhausted most standard treatments to treat their refractory disease and may even offer greater benefit if studied among less heavily treated patients as a first-line therapy for the disease.”

Source: ASH