Refractory myeloma outcomes improved by drug combination

12/12/2013

Relapsed refractory myeloma treatment outperformed standard therapy in a trial. The treatment is based on a newly approved immune modulator.

In a randomized phase III trial, the combination of pomalidomide (Pomalyst) and low-dose dexamethasone extended both progression-free and overall survival compared with high-dose dexamethasone, according to Meletios Dimopoulos, MD, of Alexandra Hospital in Athens.

Importantly, the combination was active among patients with high-risk cytogenetics, Dimopoulos reported at the annual meeting of the American Society of Hematology.

Pomalidomide plus low-dose dexamethasone got FDA approval earlier this year, based on a randomized trial comparing the drug alone with the combination.

It's indicated for patients who have failed at least two previous lines of therapy.

In the so-called MM-003 study, Dimopoulos and colleagues compared the combination with high-dose dexamethasone, which at the time was standard of care for patients who had failed two previous lines of treatment. They randomly assigned 445 patients, on a two-to-one basis, to get the combination therapy or high-dose dexamethasone.

The primary endpoint was progression-free survival, but the researchers also looked at such things as overall survival, response rates, and safety.

In particular, they studied the effect of the drugs on patients whose cancer had mutations associated with poor outcomes.

After a median follow-up of 10 months, Dimopoulos reported, the risk of progression was cut in half by the combination. (Hazard ratio 0.50, P<0.001.) Specifically, median progression-free survival was 4.0 months in the combination arm and 1.9 months among those getting just the steroid, he reported. The effect was seen even though patients who failed to respond to dexamethasone alone were allowed to cross over and take pomalidomide, Dimopoulos said.

The pomalidomide patients also enjoyed an advantage in overall survival with a median of 13.1 months versus 8.1 months for the dexamethasone patients.

The researchers also looked at outcomes for patients with some of the key mutations associated with worse outcome -- the del(17p) deletion and the t(4; 145) translocation.

Both for progression-free and overall survival, Dimopoulos said, the pomalidomide arm did better (HR 0.46 and 0.69, respectively, compared with high-dose dexamethasone.)

The study was considered sufficiently convincing that it formed the basis for European approval, noted Xavier Leleu, MD, PhD, of the Claude Huriez Hospital in Lille, France, who was not involved in the study but who moderated the session at which it was presented.

It's "definitely a very good agent," he told MedPage Today.

But he said researchers need to continue to improve treatment. "This is a good platform," he said. "The question is can we improve on it and we have some ideas on that."

 

Source: MedPage Today: http://www.medpagetoday.com/MeetingCoverage/ASHHematology/43393

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