NEW YORK (Reuters Health) – The combination of pomalidomide and low-dose dexamethasone improves survival in patients with advanced multiple myeloma more than does treatment with high-dose dexamethasone alone, a multinational study has shown.

“Pomalidomide plus low-dose dexamethasone, an oral regimen, could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma,” say the authors of the report in The Lancet Oncology published online September 3.

Dr. Jesus San Miguel, at the Clinica Universidad de Navarra in Pamplona, Spain and colleagues explain that, given alone, pomalidomide, an immunomodulatory analog of thalidomide, has little effect in patients with relapsed multiple myeloma, but a synergistic effect has been seen when given with dexamethasone.

The team conducted an open-label phase III trial comparing pomalidomide plus low-dose dexamethasone to high-dose dexamethasone alone in 455 patients with refractory or relapsed and refractory multiple myeloma, who had failed at least two previous treatments with bortezomib and lenalidomide. The participants were randomized 2:1 to the two treatment arms.

Median progression-free survival, the primary endpoint, was significantly longer with pomalidomide plus low-dose dexamethasone (4.0 months) than with high-dose dexamethasone (1.9 months). This yielded a hazard ratio of 0.48 (p<0.0001).

Median overall survival in the two arms was 12.7 months versus 8.1 months, respectively, (HR 0.74; p=0.0285), according to the report.

There were no significant differences in survival between the sexes or between patients younger or older than 65 years, the data indicate.

Regarding safety, the most common grade 3-4 hematological adverse events in the pomalidomide plus low-dose dexamethasone group and high-dose dexamethasone group were neutropenia (48% vs 16%), anemia (33% vs 37%), and thrombocytopenia (22% vs 26%).  Grade 3-4 non-hematological adverse events in the two arms included pneumonia (13% vs 8%), bone pain (7% vs 5%), and fatigue (5% vs 6%).

Discussing the results, Dr. San Miguel and colleagues conclude: “Altogether, these findings suggest that pomalidomide plus low-dose dexamethasone could be a beneficial treatment option for this patient population. Other pomalidomide-based combination treatments,” they add, “show encouraging efficacy, with 30–54% of patients achieving an overall response, and are being assessed in clinical trials.”

That information is amplified by Dr. Xavier Leleu at Hopital Claude Huriez in Lille, France, in an accompanying editorial.  “Several triplet pomalidomide-based studies are being done, and, although still preliminary, the results seem positive,” he writes.  “Pomalidomide can be used in combination with almost all existing anti-myeloma drugs because of its favourable safety profile.”

SOURCE: Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial

SOURCE: New hope for relapsed and refractory multiple myeloma

Lancet Oncol 2013.