Results of the phase III OPTIMISMM trial of pomalidomide, bortezomib, and dexamethasone

The phase III OPTIMISMM trial (NCT01734928) investigated the use of pomalidomide (P), bortezomib (V), and dexamethasone (d) against Vd in patients with relapsed/refractory multiple myeloma (RRMM). The Multiple Myeloma Hub previously reported the subanalyses results on the OPTIMISMM trial in 2020.

In this article, we summarize the final overall survival outcomes of the phase III OPTIMISMM trial published and presented by Meral Beksaç, MD from Ankara University, Turkey, during the 20th International Myeloma Society Annual Meeting in September 2023.¹

Pomalidomide, bortezomib, and dexamethasone

PVd is a preferred option in patients for whom lenalidomide (LEN) is no longer a treatment option. In the primary analysis of the phase III OPTIMISMM trial with 15.9 months of follow-up, patients with LEN-exposed RRMM had significantly prolonged median progression-free survival (PFS) with PVd versus Vd (11.2 vs 7.1 months; HR, 0.61; p < 0.0001).

OPTIMISMM trial (NCT01734928)

• Study design: An open-label, phase III trial that evaluated the efficacy and safety of PVd versus Vd in patients with RRMM who had received 1–3 prior anti-myeloma regimens
• Primary endpoint: PFS, defined as time from randomization to disease progression or death
• Median follow-up: 64.5 months
• Baseline characteristics: A total of 559 patients were included in the study, with demographics and disease characteristics well-balanced between arms (PVd, n = 281; Vd, n = 278). All patients were previously exposed to LEN, and 71% versus 69% in the PVd and Vd arms, respectively, were LEN-refractory.

Results¹

Treatment duration

• Drug exposure was approximately twice as long in patients treated with PVd versus V, with a mean treatment duration of 76.3 weeks versus 38.8 weeks.

Overall survival

Overall survival (OS) was compared between arms using a log-rank test and the Kaplan-Meier method. A pre-planned exploratory analysis of OS was conducted using the Cox proportional hazards model to analyze subsequent treatment arms in patients who were allocated to the PVd versus Vd arms.

• In the intention-to-treat population, there was no significant difference in median OS in patients treated with PVd versus Vd (35.6 months vs 31.6 months; HR, 0.94; p = 0.571).
• In the subgroup analysis, there was a trend for most subgroups – including high-risk patients and patients with high beta-2-microglobulin – to benefit from PVd versus Vd. However, no significant difference was observed.

Progression-free survival and second PFS (PFS2)

• PFS was significantly longer in the PVd versus Vd arm (11.7 months vs 6.9 months; HR, 0.56; p < 0.0001), consistent with the primary analysis.
• Median PFS2, which has not been previously reported, was longer in patients treated with PVd versus Vd (22.1 months vs 16.9 months; HR, 0.77; p = 0.008).

Safety¹

• Infections were seen in both the PVd and Vd arms.
• Beksaç highlighted side effects of importance, including peripheral sensory neuropathy and thrombocytopenia being similar in both arms, and neutropenia being more frequent in the PVd arm versus Vd arm (131 vs 24 patients with Grade 3/4 neutropenia).

• The primary treatment-emergent adverse event leading to treatment discontinuation was peripheral sensory neuropathy.

Conclusion

The final analysis of the phase III OPTIMISMM trial supports the use of PVd as an effective treatment option in patients with RRMM.