Successful Phase III OPTIMISMM study, of Pomalyst + bortezomib + dexamethasone for multiple myeloma.- Celgene.

Celgene Corporation has announced results from the OPTIMISMM study, a phase III, randomized, open-label, international clinical study of the investigational combination regimen of Pomalyst/Imnovid (pomalidomide), bortezomib (Velcade) and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) who had received at least one prior treatment including lenalidomide. The results were presented at the 54th Annual American Society of Clinical Oncology Scientific Sessions (ASCO) in Chicago, Illinois on June 1-5, 2018 .

OPTIMISMM study evaluated the efficacy and safety of Pomalyst/Imnovid (pomalidomide) plus bortezomib and low-dose dexamethasone (PVd) versus bortezomib and low-dose dexamethasone (Vd) in patients with early RRMM (1-3 prior lines of therapy). It is the only phase III trial to report results with a triplet combination in patients who have all received prior lenalidomide therapy. With lenalidomide becoming a standard of care, this represents a patient population for which there is a growing unmet medical need. An analysis of the results found that the treatment with PVd resulted in significantly improved progression-free survival (PFS) and an earlier, deeper, more durable response in these patients compared to Vd treatment. The study, which included a high percentage of patients refractory to lenalidomide (71% in the PVd arm, 69% in the Vd arm), met its primary endpoint of PFS. Those receiving PVd achieved a statistically significant longer PFS than those in the Vd treatment arm (11.20 months vs. 7.10 months, respectively [P= < .0001, HR 0.61; 95% CI: (0.49-0.77)]), reducing the risk of disease progression or death by 39% in the PVd arm. The PFS benefit was observed in the following subgroups of patients: LEN-refractory, LEN-nonrefractory, prior PI exposure or high-risk cytogenetics. Overall response rate (ORR), one of the study's secondary endpoints, was also significantly higher in the PVd treatment arm, compared to those receiving Vd (82.2% vs. 50.0%, p < 0.001). Additionally, time to treatment response was longer in the PVd arm (0.9 months PVd vs. 1.4 months Vd), complete response was higher in the PVd arm (15.7% PVd vs. 4.0% Vd) and those receiving PVd experienced a longer duration of response than those in the Vd arm (13.7 months PVd vs. 10.9 months Vd.) In an exploratory sub-group analysis, patients who had received one prior line of therapy reported longer PFS (20.73 months in PVd arm (n=40) vs. 11.63 months in Vd arm (n=41)) and ORR (90.1% in PVd arm vs. 54.8% in Vd arm) with a 46% reduction in the risk of disease progression or death in the PVd treatment arm compared with Vd. Other secondary endpoints included overall survival and safety.

The most common Grade 3/4 treatment-emergent adverse events (TEAE) were neutropenia (PVd: 42% vs. Vd: 9%), infections (PVd: 31% vs. Vd: 18%) and thrombocytopenia (PVd: 27% vs. Vd: 29%.) Rates of grade 3 or 4 deep vein thrombosis in the PVd vs. Vd arms were 0.7% vs. 0.4% and rates of grade 3 or 4 pulmonary embolism in PVd vs. Vd were 4.0% vs. 0.4%. No events were fatal. SPMs occurred in 3.2% (2.7 per 100 person years) of patients treated with PVd and 1.5% (1.2 per 100 person years) of patients treated with Vd. The most common reason for treatment discontinuation was progressive disease.