Dr Beksac on OS Data From the OPTIMISMM Trial in Relapsed/Refractory Multiple Myeloma

Meral Beksac, MD, director of Department of Hematology, Ankara University, Turkey, discusses overall survival (OS) data from the phase 3 OPTIMISMM trial (NCT01734928) in patients with relapsed/refractory multiple myeloma.

OPTIMISMM evaluated the addition of pomalidomide (Pomalyst) to bortezomib (Velcade) and dexamethasone (PVd; n = 281) vs Vd alone (n = 278) in patients with relapsed/refractory multiple myeloma. To be eligible for enrollment, patients had to be at least 18 years of age, have an ECOG performance status between 0 and 2, and exposure to at least 1 but no more than 3 prior regimens, including a lenalidomide (Revlimid)-containing regimen for at least 2 consecutive cycles. Earlier results previously published in Lancet Oncology with a median follow-up of 15.9 months (interquartile range, 9.9-21.7) demonstrated that PVd led to a significant improvement in median progression-free survival compared with Vd alone, at 11.20 months (95% CI, 9.66-13.73) vs 7.10 months (95% CI, 5.88-8.48), respectively (HR, 0.61, 95% CI, 0.49-0.77; P < .0001). These results crossed the prespecified threshold for significance, meeting the primary end point of the trial, Beksac explains.

Findings from the first and final analysis for OS were presented at the 2023 IMS Annual Meeting. With a data cutoff of May 13, 2022, at a median follow-up of 64.5 months, investigators confirmed that PFS remains statistically significant (HR, 0.56; 95% CI, 0.46-0.68; P < .0001). However, PVd failed to demonstrate a statistically significant improvement in OS compared with Vd (HR, 0.94; 95% CI, 0.77-1.15; P = .571), though investigators noted numerical improvement of 4 months at 35.6 months for PVd and 31.6 months for Vd, Beksac says.

Notably, the median treatment exposure with PVd was double that with Vd alone, at 41.2 months (range, 1.1-355.4) and 21.4 months (range, 0.4-324.4), respectively. Additionally, more patients in the control arm received subsequent treatment, most of whom received pomalidomide-based regimens, Beksac says. As such, though not intended, the study mirrored that of a crossover design, which may potentially explain the similarity in survival outcomes, Beksac says. Notably, following a subsequent time-dependent covariate analysis that accounted for the confounding factor of second-line therapy, investigators were able to show a statistically significant P value of .008 favoring the triplet arm, Beksac concludes.