Chicago, IL—The triplet regimen of pomalidomide (Pomalyst), bortezomib (Velcade), and low-dose dexamethasone (PVd) significantly extended progression-free survival (PFS) compared with the doublet of bortezomib plus dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma who had previously received lenalidomide (Revlimid) therapy, according to new data presented at ASCO 2018.
The results of the phase 3 OPTIMISMM clinical trial showed a 39% risk reduction in disease progression or death with PVd compared with Vd, said Paul G. Richardson, MD, Clinical Program Leader, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston.
These results "support the use of PVd in first relapse in patients with relapsed or refractory multiple myeloma and prior exposure to lenalidomide," Dr Richardson said. Pomalidomide is approved by the FDA for the treatment of relapsed or refractory multiple myeloma after ≥2 therapies, including lenalidomide, an immunomodulator. Furthermore, in patients with lenalidomide-refractory disease, the use of pomalidomide treatment has demonstrated an overall survival (OS) advantage.
Triplet combinations of pomalidomide, bortezomib, and dexamethasone have demonstrated encouraging activity in patients with lenalidomide-refractory disease.
"With the recent approval of lenalidomide as maintenance by the FDA, it's become very important to understand what benefits most patients for whom lenalidomide is no longer a treatment option and are progressing on lenalidomide therapy," said Dr Richardson.
The OPTIMISMM Study
The OPTIMISMM clinical trial included 559 patients who had received 1 to 3 previous lines of therapy and ≥2 cycles of lenalidomide therapy. All patients were randomized to the PVd or Vd regimen.
In 21-day cycles, patients in the triplet arm received pomalidomide 4 mg daily on days 1 to 14; bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of cycles 1 to 8, and on days 1 and 8 of cycles 9 and higher; and dexamethasone 20 mg daily (10 mg for those aged >75 years) on the days of, and after, receiving bortezomib.
The baseline characteristics were generally well-balanced between the 2 arms (median age, approximately 68 years). Approximately 20% of patients in each arm had high-risk cytogenetics (del17p, t[4;14], and/or t[14;16]).
Approximately 70% of patients had lenalidomide-refractory disease, and 9% of patients who received PVd and 12% of those who received Vd had disease progression with bortezomib maintenance therapy. Approximately 70% of patients had disease refractory to their last previous regimen.
The median treatment duration was almost twice longer with PVd than with Vd (8.8 months vs 4.9 months, respectively). The most common reason for treatment discontinuation was progressive disease, which was 39.1% in the PVd arm and 47.1% in the Vd arm.
With a median follow-up of 16 months, the median PFS was 11.2 months in the PVd arm and 7.1 months in the Vd arm (hazard ratio [HR], 0.61; P <.0001). The PFS advantage with PVd was observed across patient subgroups and regardless of lenalidomide-refractory status, and was maintained through the next line of therapy.
In patients who received only 1 previous line of therapy, the advantage with adding pomalidomide to the treatment regimen was even greater: a median PFS of 20.7 months versus 11.63 months with Vd (HR, 0.54; P = .0027).
In the lenalidomide-refractory subgroup, the median PFS was 9.53 months in the PVd arm versus 5.59 months in the Vd arm (HR, 0.65; P <.001). In patients who were exposed to lenalidomide but did not have disease refractory to lenalidomide, "the difference was more striking," said Dr Richardson—with a median PFS of 22.0 months with PVd and 11.6 months with Vd (HR, 0.48; P = .001). The OS data were not mature at the time of the presentation.
The overall response rate (ORR) was significantly higher with PVd (82.2%) versus Vd (50%). In patients with only 1 previous line of therapy, the ORR was 90.1% with PVd versus 54.8% with Vd.
"PVd led to deeper responses, with higher stringent complete response or complete response, and more very good partial responses than Vd," Dr Richardson said.
Furthermore, the time to next therapy was extended significantly with the addition of pomalidomide, from 8.5 months to 22.2 months (HR, 0.42; P <.001).
The safety profile with PVd was consistent with known toxicities associated with pomalidomide and low-dose dexamethasone. The most common grade 3 or 4 treatment-emergent adverse events that occurred more often with PVd than Vd were neutropenia (42% vs 9%, respectively) and infections (31% vs 18%, respectively).