An overall survival (OS) benefit has been shown in an interim analysis of the phase 3 clinical trial known as MM-003, which is evaluating pomalidomide (a next-generation oral immunomodulatory agent) plus low-dose dexamethasone in patients with multiple myeloma whose disease relapsed or recurred after at least 2 previous lines of therapy.
In MM-003, patients were randomized to pomalidomide plus low-dose dexamethasone or high-dose dexamethasone alone. The Data Safety Monitoring Board (DSMB), which analyzed the interim data and determined that there was a survival benefit in the experimental arm, recommended that patients who had not yet progressed in the high-dose dexamethasone arm be crossed over to the pomalidomide plus low-dose dexamethasone arm.
The DSMB also found that the drug’s safety profile was consistent with previous studies of pomalidomide in patients with pretreated myeloma.
The DSMB determined that MM-003 met the primary end point of improvement in progression-free survival (PFS) at the final analysis for that outcome. In addition, at the interim OS analysis—a key secondary end point—the study crossed the superiority boundary; the study was also powered to evaluate the OS benefit.
Improvements in PFS and OS were both “highly statistically significant and clinically meaningful,” according to a press release from Celgene, the manufacturer of this medication. The full data are being prepared for submission for presentation at a future medical meeting and were not publicized.
“The survival results in this study build on earlier observations of high response rates for pomalidomide and dexamethasone in multiple myeloma patients who had been exposed to multiple therapies, including immunomodulatory agents and proteasome inhibitors,” said the principal investigator of MM-003, Jesus San Miguel, MD, Head of the Department of Hematology at the University of Salamanca, Spain.
“The continued progress of new agents in this area of disease, particularly in late-stage patients, is critical as we look to extend remissions and survival for these individuals,” Dr San Miguel noted.
Patients in the pomalidomide arm received 4 mg of pomalidomide on days 1 through 21 of each 28-day cycle, plus dexamethasone. The dexamethasone dose was determined by the patient’s age: those aged ≤75 years received 40 mg of oral low-dose dexamethasone, and patients aged >75 years received 20 mg on days 1, 8, 15, and 22 of each cycle, until disease progression.
Patients in the control arm aged ≤75 years received 40 mg of oral high-dose dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle; younger patients received 20 mg on the same schedule, until progression.
Looking for Regulatory Approval
MM-003 is being conducted as part of the company’s regulatory application to market the drug in Europe. The European Medicines Agency is currently reviewing the application for pomalidomide in combination with dexamethasone for patients with pretreated relapsed and refractory multiple myeloma, and a decision is expected in the second half of 2013.
The US Food and Drug Administration’s (FDA) Oncology Drug Advisory Committee is also scheduled to review Celgene’s application for pomalidomide in February 2013. If the MM-003 trial results are submitted for consideration as part of the New Drug Application (NDA) to the FDA, this would extend by 6 months the FDA’s deadline to rule on the NDA.
Meanwhile, pomalidomide is available through Celgene’s expanded access program, PEXIUS, for patients with relapsed and refractory myeloma who lack other treatment options. PEXIUS is designed as a multicenter, single-arm, open-label program that does not compare the treatment with another regimen.
Pomalidomide is also being evaluated for the treatment of myelofibrosis.