Pomalidomide in combination with low-dose dexamethasone had a highly significant benefit on progression-free survival and overall survival compared with single-agent high-dose dexamethasone in patients with relapsed or refractory multiple myeloma, according to updated results of the MM-03 trial presented at the ASCO 2013 Annual Meeting.
CHICAGO-Pomalidomide in combination with low-dose dexamethasone had a highly significant benefit on progression-free survival and overall survival compared with single-agent high-dose dexamethasone in patients with relapsed or refractory multiple myeloma, according to updated results of the MM-03 trial presented at the ASCO 2013 Annual Meeting.
“In light of this advantage, pomalidomide plus low-dose dexamethasone should be considered a new standard of care for the treatment of relapsed or refractory patients after treatment with lenalidomide and bortezomib,” said presenter Katja Weisel, MD, of the University Hospital Tuebingen, Germany.
Earlier this year, the FDA approved pomalidomide for the treatment of patients with relapsed or refractory multiple myeloma who have failed at least two prior therapies including lenalidomide and bortezomib.
MM-03 included 455 patients with relapsed or refractory multiple myeloma who were randomly assigned 2:1 to treatment with pomalidomide plus low-dose dexamethasone (n = 302) or high-dose dexamethasone (n = 153). All patients had to be refractory to their last prior therapy and have failed lenalidomide and bortezomib after receiving two or more consecutive cycles of each.
The median number of prior therapies among patients was five, with 72% of patients refractory to lenalidomide and bortezomib.
With a median follow-up of 10 months, the researchers have a confirmed highly significant benefit of pomalidomide on progression-free survival, with the median duration of 4 months vs 1.9 months in patients on high-dose dexamethasone.
According to Dr. Weisel, this benefit extended over all of the analyzed subgroups including those patients with double refractory disease, as well as patients with bortezomib and lenalidomide as the last prior treatment line.
Patients assigned to pomalidomide also had a significantly improved overall survival. The median overall survival on the combination was 12.7 months vs. 8.1 months. This difference was also maintained in all subgroups analyzed.
At the time of the overall survival analysis, only 7% of patients in the high-dose dexamethasone group remained on treatment. Fifty percent of patients had crossed over to treatment with pomalidomide.
“The overall response rate was 31% for pomalidomide plus low-dose dexamethasone compared with 10% in the high-dose dexamethasone group, with a few good partial and complete remissions,” Dr. Weisel said.
The main toxicity of pomalidomide was hematologic, with grade 3/4 neutropenia occurring in 48% of patients; however, this led to only a few febrile complications, Dr. Weisel said. The main grade 3/4 non-hematologic event was infection.
“The important message here is that if you do not get a partial response or a complete response, don’t throw the therapy away. These minor benefits may actually translate into significant long-term clinical benefits,” said discussant Sagar Lonial, MD, of the Winship Cancer Institute at Emory University. “It is a different situation than when discussing a newly diagnosed patient where the goal should ultimately be complete response.”