OPTIMISMM is the only phase III trial to show a significant PFS benefit in R/R MM patients with prior exposure to lenalidomide.
Patients with relapsed or refractory multiple myeloma exposed to prior lenalidomide had significant improvements in progression-free survival (PFS) when treated with the combination of pomalidomide, bortezomib, and low-dose dexamethasone (PVd), compared with patients who received bortezomib and low-dose dexamethasone (Vd) alone, according to the results of the phase III OPTIMISMM trial (abstract 8001). Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, presented the study results at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO), held June 1–5 in Chicago.
“This study investigated a clinically relevant and growing patient population who received upfront lenalidomide but for whom lenalidomide is no longer a treatment option,” said Richardson. “These results support the use of PVd in first relapse in patients with relapsed/refractory multiple myeloma and prior to exposure to lenalidomide.”
According to Richardson, pomalidomide is the most potent approved oral immunomodulatory drug available, and it has direct activity against myeloma. In a preclinical study, pomalidomide was shown to inhibit proliferation of lenalidomide-resistant cells. In addition, it is approved in combination with low-dose dexamethasone for relapsed/refractory disease in patients with multiple myeloma who have received two or more prior therapies.
More recently, lenalidomide has become a mainstay of upfront treatment of myeloma, and the US Food and Drug Administration recently approved lenalidomide as a maintenance treatment. Therefore, treatment options are needed for patients for whom lenalidomide is no longer an option.
OPTIMISMM included 559 patients with relapsed or refractory myeloma who had received one to three prior lines of treatment and more than two cycles of prior lenalidomide. Patients were randomly assigned to receive PVd or Vd. Baseline characteristics were well balanced between arms, including high-risk cytogenetics. Almost three-quarters of patients were lenalidomide-refractory.
Median treatment duration was 8.8 months for PVd, compared with 4.9 months for Vd. After a median follow-up of 15.9 months, with PVd there was a significant 39% reduction in risk for progression and death, compared with Vd. The median PFS was 11.2 months for PVd and 7.1 months for Vd (P < .0001).
When the investigators evaluated patients with one prior line of therapy, the results were even more encouraging, Richardson said. PVd reduced the risk of progression and death by 46% compared with Vd. Median PFS was 20.73 months with PVd and 11.63 months with Vd (P = .0027).
In the intent-to-treat group, there was a significant difference in overall response rate (ORR), with rates of 82.2% in the PVd arm and 50.0% in the Vd arm (P < .001). The ORR was also better with PVd among patients who had received one prior line of therapy (90.1% vs 54.8%; P < .001).
Among subgroups, including age, performance status, and number of prior therapies, data remained in favor of the triplet compared with the doublet. This also applied to type of prior therapies, Richardson noted.
Looking at lenalidomide-refractory disease, there remained a statistically significant and clinically important difference in PFS. The median PFS in lenalidomide-refractory patients assigned to PVd was 9.53 months, compared with 5.59 months for Vd (P < .001). The difference was even more striking in patients who were lenalidomide-exposed but not refractory (HR, 0.48), Richardson said.
Patients receiving PVd had longer treatment exposure compared with Vd. There was more neutropenia and infection with triplet therapy compared with doublet therapy. Second primary malignancy occurred in 3.2% of patients treated with PVd, compared with 1.5% of patients in the Vd arm.