Celgene Issues Results of Phase III Study on Pomalidomide Plus Low-Dose Dexamethasone

Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation

, today announced that updated results from MM-003, a phase III multi-center, randomized open-label study (n=455) of pomalidomide (marketed as POMALYST^® in the U.S. and IMNOVID^® in the E.U.) plus low-dose dexamethasone, were published online ahead of print in The Lancet Oncology. The study compared oral pomalidomide plus low-dose dexamethasone with high-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma who have failed at least two prior therapies with both bortezomib and lenalidomide, administered alone or in combination. At the interim analysis (ASH 2012, median follow-up 4.2 months), the study met its primary endpoint as pomalidomide plus low-dose dexamethasone demonstrated a significant improvement in progression-free survival (PFS) (3.8 months vs 1.9 months HR 0.41 p<0.0001) compared with high-dose dexamethasone. There was also a significant improvement in the key secondary endpoint of overall survival (OS) (11.9 months vs 7.8 months HR 0.53 p<0.0002) compared with high-dose dexamethasone even though 45 patients in the high-dose dexamethasone arm crossed over and received pomalidomide. Additionally, the Data Monitoring Committee recommended that patients who had not yet progressed in the high-dose dexamethasone arm should have access to pomalidomide with or without low-dose dexamethasone. At a median follow-up of 10.0 months, an updated PFS analysis and final OS analysis were conducted. Pomalidomide plus low-dose dexamethasone continued to demonstrate significantly longer PFS, the primary endpoint, compared with high-dose dexamethasone (4.0 months vs. 1.9 months, HR=0.48, p<0.0001). Additionally, pomalidomide plus low-dose dexamethasone demonstrated a significant improvement in OS compared with high-dose dexamethasone (12.7 months vs. 8.1 months, HR=0.74, p=0.0285). Overall response rate for patients receiving pomalidomide plus low-dose dexamethasone was 31% compared with 10% for patients receiving high-dose dexamethasone (p<0.0001). The most common grade 3-4 hematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone arms, respectively, were: neutropenia (48% 143/300 vs. 16% 24/150), anemia (33% 99/300 vs. 37% 55/150) and thrombocytopenia (22% 67/300 vs. 26% 39/150). Grade 3-4 non-hematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone arms, respectively, included: pneumonia (13% 38/300 vs. 8% 12/150), bone pain (7% 21/300 vs. 5% 7/150) and fatigue (5% 16/300 vs. 6% 9/150). Four patients in the pomalidomide plus low-dose dexamethasone arm and one patient in the high-dose dexamethasone arm developed second primary malignancies. Of these, two patients in the pomalidomide plus low-dose dexamethasone arm had invasive solid tumor cancers and two patients in this group and the one in the high-dose dexamethasone group had non-invasive cancers (basal-cell skin cancers). Treatment-related adverse events led to treatment discontinuation in 4% of patients in the pomalidomide plus low-dose dexamethasone arm and 6% of patients in the high-dose dexamethasone arm. Patients in the pomalidomide plus low-dose dexamethasone arm received 4 mg of oral pomalidomide on days 1-21 of each 28-day cycle. Oral dexamethasone was given at 40 mg on days 1, 8, 15, and 22); for patients older than 75 years, dexamethasone was administered at 20 mg weekly. Patients in the comparator arm were treated with 40 mg oral high-dose dexamethasone on days 1-4, 9-12 and 17-20 of each 28-day cycle, until disease progression; patients older than 75 years received 20 mg oral dexamethasone on the same schedule. Results of the MM-003 trial formed the basis of an August 2013 approval by the European Medicines Agency in patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including both lenalidomide and bortezomib and have demonstrated disease progression on the last therapy.