KEY TAKEAWAYS
- The OPTIMISMM phase III trial aimed to compare the OS of patients treated with PVd versus Vd.
- The secondary endpoint was OS.
- The study suggested PVd may improve survival and disease control in r/r MM, with a manageable safety profile.
Pomalidomide is effective in multiple myeloma(MM), especially for patients who have received prior therapies, including lenalidomide(LEN) and bortezomib(BORT). The PVd regimen (pomalidomide, bortezomib, and dexamethasone) significantly prolonged progression-free survival(PFS) compared to bortezomib plus dexamethasone(DEX) in the OPTIMISMM study.
Researchers aimed to compare the OS of patients treated with PVd versus Vd. Patients eligible for the study had a diagnosis of relapsed/refractory multiple myeloma(RRMM), had undergone 1–3 prior lines of therapy (including at least one LEN-containing regimen), and had an ECOG performance status of ≤2.
Documented disease progression during or after the last anti-myeloma therapy was required. Overall survival (OS) served as a secondary endpoint, the time from randomization to death from any cause. OS was statistically compared using a log-rank test (with an overall 2-sided significance level of 5%), stratified by the three baseline factors used for randomization.
The Kaplan–Meier method estimated survival distribution functions for each arm, providing median OS and 2-sided 95% CI. Additionally, a Cox proportional hazards model, stratified by the three baseline factors, was utilized to estimate HR and their corresponding 95% CIs. In the intent-to-treat(ITT) population (N=559), 281 and 278 patients were receiving PVd and Vd treatment, respectively, with median treatment durations of 41.2 and 21.4 months.
In this final OS analysis with mature data (overall event rate, 70.0%), and a median follow-up of 64.5 months for surviving patients (data cutoff May 13, 2022), PVd demonstrated a numerically longer median OS compared to Vd (35.6 vs 31.6 months; HR [95% CI], 0.94 [0.77–1.15]; P=0.571). Median PFS2 was also longer in patients treated with PVd versus Vd (22.1 vs 16.9 months; HR [95% CI], 0.77 [0.64–0.94]; nominal P=0.008). Updated PFS and safety data remained consistent with the primary analysis. PVd showed longer time to treatment failure compared to Vd (8.8 vs 4.6 months).
The most common treatment-emergent adverse events (TEAEs) with PVd included neutropenia (54%), peripheral sensory neuropathy (48%), and thrombocytopenia (40%), while with Vd, these were thrombocytopenia (39%), peripheral sensory neuropathy (38%), and diarrhea (31%). Peripheral neuropathy was the most common TEAE leading to treatment discontinuation (PVd, 11%; Vd, 8%). Death occurred in 196 (71%) patients treated with PVd and 190 (70%) patients treated with Vd.
The study suggested PVd may improve survival and disease control in r/r MM, with a manageable safety profile.
Source: https://imsannual2023.eventscribe.net/fsPopup.asp?PresentationID=1302324&mode=presInfo
Clinical Trial: https://clinicaltrials.gov/study/NCT01734928
Beksac M, et al. Pomalidomide, bortezomib, and dexamethasone vs bortezomib and dexamethasone in relapsed or refractory multiple myeloma (OPTIMISMM): final survival outcomes from a randomized, open-label, phase 3 trial.
