Pomalidomide, an immunomodulatory drug, combined with low-dose dexamethasone improved progression-free survival in patients with refractory or relapsed and refractory multiple myeloma compared with standard of care high-dose dexamethasone, according to the results of a multicenter, open-label, phase III trial.
Although prior research has shown that pomalidomide has efficacy in patients refractory to lenalidomide and bortezomib, it had not yet been compared with existing standard of care treatments in relapsed or refractory myeloma.
Jesus San Miguel, MD, PhD, of University Hospital of Salamanca, Salamanca, Spain, and colleagues enrolled patients with refractory or relapsed and refractory myeloma who had failed at least two prior treatments with bortezomib and lenalidomide. Patients were randomly assigned 2:1 to receive pomalidomide plus low-dose dexamethasone (n = 302) or high-dose dexamethasone (n = 153). The results were published in the Lancet Oncology.
Patients were followed for a median of 10 months. At that time, the median progression-free survival was 4 months for patients treated with pomalidomide compared with 1.9 months for high-dose dexamethasone (HR = 0.48; 95% CI, 0.39–0.60; P < .0001). In addition, results of the final overall survival analysis showed that the overall survival was significantly longer with pomalidomide (12.7 months) compared with high-dose dexamethasone (8.1 months; HR = 0.74; 95% CI, 0.56–0.97; P = .0285).
Treatment with pomalidomide was generally well-tolerated with 9% of patients discontinuing the drug because of adverse events.
The researchers wrote that one of the weaknesses of the study included its open-label design.
“Additionally, the unmasked nature of the study may have affected the updated PFS analysis in favor of the high-dose dexamethasone group because nine patients crossed over before progressive disease,” the researchers wrote. “Furthermore, the crossover of patients receiving high-dose dexamethasone without progressive disease to receive pomalidomide unblinded is expected to have reduced the magnitude of the difference in overall survival between the treatment groups from the interim to the final overall survival analysis.”
Accompanying editorialist Xavier Leleu, MD, PhD, of the Centre Hospitalier Regional Universitaire, Lille, France, described pomalidomide as a promising new agent in the myeloma arena for its efficacy in patients with refractory or relapsed and refractory disease. In addition, the drug has shown promise for improved quality of life and its use in patients with renal insufficiency, he wrote.
“The effect of pomalidomide on the quality of life will be described in a subsequent report, but it seems logical to assume that the oral availability of pomalidomide, rapid onset of response, increased depth of response and prolonged survival will improve the quality of life of patients with refractory or relapsed and refractory myeloma,” Leleu wrote. “Moreover, although the dose modification definition of pomalidomide according to the creatinine clearance is still ongoing, preliminary reports suggest it might not be necessary to modify the dose of pomalidomide in renal insufficiency. This is an important consideration because patients with advanced myeloma frequently have renal insufficiency that often requires a dose adaptation for many drugs.”