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