CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.
Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator, of the Dana-Farber Cancer Institute in Boston.
The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.
Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.
“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.
Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.
Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.
In thetrial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.
Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).
Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).
The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).
The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).
The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.
Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.
PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.
The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.
SOURCE: Richardson PG et al. ASCO 2018, .