Results from the OPTIMISMM study, a phase III, randomised, open-label, international clinical study of the investigational combination regimen of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) who had received at least one prior treatment including lenalidomide, were presented at the 23rd Annual European Haematology Association (EHA).

Prof Paul Richardson spoke with ecancer to discuss these findings.

OPTIMISMM evaluated the efficacy and safety of 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.

In the UK, over 16,000 patients have been treated with lenalidomide since 2009;[iii] this represents a patient population for which there is a growing unmet medical need.

“Results from OPTIMISMM are promising and show the potential of pomalidomide in combination with other therapies, earlier in the myeloma treatment pathway. For patients with myeloma, there is real concern about relapse and a range of effective treatments that can delay relapse and potentially be available in the future is of the utmost importance,” said Dr Neil Rabin, Consultant Haematologist at University College London Hospitals. “There is a growing unmet need for those patients who have been treated previously with lenalidomide, and combination therapies are key to meet that need. These data are therefore very encouraging.”

An analysis of the results found that the treatment with PVd resulted in significantly improved progression-free survival (PFS) 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.1

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 shorter 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=111) vs. 11.63 months in Vd arm (n=115)) 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.

Commenting on the results, Myeloma UK Director of Research, Dr Simon Ridley said: “Results from OPTIMISMM provide hope to the myeloma community. While myeloma is still an incurable cancer, there are a growing number of treatments, and combinations that can achieve promising results and enable patients to stay in remission for longer. We hope that new data from trials such as OPTIMISMM can enable patients to access effective treatment combinations in future.”

The most common grade 3/4 treatment-emergent adverse events (TEAE) in the safety population (PVd n= 278. Vd n=270) 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.

Second Primary Malignancies (SPM) 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.

Source: Reynolds Mackenzie