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Positive Phase III Results for Revlimid Plus Low-Dose Dexamethasone in Refractory Multiple Myeloma

FDA review set for February 2013 (Dec. 11)

Results have been reported from a phase III, randomized, open-label study (MM-003) of pomalidomide (Revlimid, Celgene) plus low-dose dexamethasone compared with high-dose dexamethasone alone in patients with refractory multiple myeloma who failed treatment with both bortezomib and lenalidomide, administered either alone or in combination. The new data were presented at the 54th American Society of Hematology annual meeting.

The MM-003 trial met its primary endpoint of improvement in progression-free survival (PFS). PFS was significantly longer in patients who received pomalidomide plus low-dose dexamethasone compared with those who received high-dose dexamethasone (median: 3.6 months vs. 1.8 months, respectively; hazard ratio [HR]: 0.45; P < 0.001).

An interim analysis of overall survival (OS) was also conducted. In this assessment, pomalidomide plus low-dose dexamethasone demonstrated a significant improvement in OS versus high-dose dexamethasone (median OS not reached vs. 7.8 months, respectively; HR: 0.53; P < 0.001). As a result, the Data Monitoring Committee recommended that patients who had not yet progressed in the high-dose dexamethasone arm should be crossed over to pomalidomide plus low-dose dexamethasone.

Pomalidomide plus low-dose dexamethasone also demonstrated a significantly greater overall response rate compared with high-dose dexamethasone (21% vs. 3%, respectively; P < 0.001). A subset of patients who were treated for at least 6 months showed a greater overall response rate (24% vs. 3%; P < 0.001). Further evaluation of response rates is ongoing.

The most common grades-3 and -4 hematologic toxicities in the pomalidomide plus low-dose dexamethasone arm and the high-dose dexamethasone arm included neutropenia (42% vs. 15%, respectively), anemia (27% vs. 29%), thrombocytopenia (21% vs. 24%), and febrile neutropenia (7% vs. 0%). Other toxicities (grade 3 or 4) were predominantly infections (24% vs. 23%), pneumonia (9% vs. 7%), hemorrhage (3% vs. 5%), glucose intolerance (3% vs. 7%), and fatigue (5% vs. 5%). The primary reason for discontinuation was progressive disease — 35% in the pomalidomide plus low-dose dexamethasone arm and 49% in the high-dose dexamethasone arm. The proportions of patients who discontinued because of adverse events were 7% versus 6%, respectively.

Patients in the pomalidomide plus low-dose dexamethasone arm received 4 mg of oral pomalidomide on days 1 to 21 of each 28-day cycle. Oral dexamethasone was administered at 40 mg weekly; for patients older than 75 years, dexamethasone was administered at 20 mg weekly.

Patients in the comparator arm were treated with 40 mg of oral high-dose dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle until disease progression; patients older than 75 years received 20 mg of oral dexamethasone on the same schedule.

A new drug application (NDA) for pomalidomide plus low-dose dexamethasone has been accepted for review by the FDA, with a Prescription Drug User Fee Act (PDUFA) date of February 10, 2013.

Source: Celgene International Sàrl; December 11, 2012.

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