CHICAGO—The addition of pomalidomide to bortezomib and low‐dose dexamethasone (PVd) significantly improves progression-free survival (PFS) in lenalidomide-exposed patients with relapsed or refractory (R/R) multiple myeloma (MM), a new study reveals.
Up until now, pomalidomide and dexamethasone (Pd) had been the only therapy investigated exclusively after lenalidomide therapy, according to Paul G. Richardson, MD.
Now, he said, “a triple combination of PVd demonstrated promising activity in early phase clinical trials of lenalidomide-refractory patients.”
Dr Richardson, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented the findings of the phase 3 OPTIMISMM trial (Abstract 8001) at the American Society of Clinical Oncology Annual Meeting.
The oral immunomodulatory agent pomalidomide, a standard-of-care treatment in R/R MM, has demonstrated synergistic anti-myeloma activity with dexamethasone and proteasome inhibitors.
A combination of pomalidomide and dexamethasone is indicated for MM patients after 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.
“Lenalidomide is an established therapy in newly diagnosed multiple myeloma,” he explained. “Therefore, patients for whom lenalidomide is no longer a treatment option represent a clinically relevant population with unmet need.”
Phase 3 OPTIMISMM trial (NCT01734928)
Dr Richardson reported the final PFS and safety data from the first phase 3 pomalidomide triplet trial comparing PVd against bortezomib and dexamethasone (Vd) in an entirely post-lenalidomide treated population.
The 559 patients had 1 to 3 prior lines of therapy and 2 or more cycles of prior lenalidomide. They were randomized to receive PVd (281 patients, median age 67 years) or Vd (278 patients, median age 68 years).
In 21-day cycles, patients received pomalidomide 4 mg per day on days 1-14 (PVd arm only); bortezomib 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1-8 and on day 1 and 8 of cycles 9 and higher; and dexamethasone 20 mg per day (10 mg for those over age 75) on the days of and after bortezomib.
The primary endpoint was PFS.
After a median follow-up of 16 months, “PVd reduced the risk of progression or death by 39% compared with Vd,” Dr Richardson said.
Median PFS was 11.2 months in the PVd group and 7.1 months in the Vd group. Overall survival data are not mature.
The overall response rate was significantly higher with PVd (82.2%) vs Vd (50%).
And the overall response rate was even higher in patients with only 1 prior line of therapy (90.1% vs 54.8%, respectively).
“PVd led to deeper responses with higher stringent complete response/complete response and more very good partial responses than Vd,” Dr Richardson noted.
“PFS was improved with PVd vs Vd across patient subgroups and regardless of lenalidomide refractoriness,” he added. “The PFS benefit with PVd was maintained through the next line of therapy.”
He reported longer treatment duration and exposure with PVd compared with Vd.
The safety profile was consistent with known toxicities associated with pomalidomide and low-dose dexamethasone, he said.
Most common grade 3/4 treatment-emergent adverse events were higher with PVd than Vd, including neutropenia (42% vs 9%) and infections (31% vs 18%).
In conclusion, Dr Richardson said, “These results support the use of PVd in first relapse in patients with relapsed/refractory multiple myeloma and prior exposure to lenalidomide.”
Future analyses of the data will include correlatives, minimal residual disease, and quality of life, he said.
The trial was sponsored by Celgene.