Network Meta-Analysis of Once Weekly Selinexor-Bortezomib-Dexamethasone in Previously Treated Multiple Myeloma

Abstract

Background: Despite the availability of new treatments, multiple myeloma (MM) is an incurable cancer with nearly all patients relapsing and undergoing multiple lines of treatment. Performing head-to-head comparisons of all treatment options is not feasible. Thus, network meta-analyses play an important role in allowing health-care decision makers to compare the effectiveness of treatment options. Objectives: A Bayesian network meta-analysis (NMA) was developed from studies identified from a systematic literature review (SLR) to evaluate the efficacy of once weekly oral selinexor with once weekly bortezomib and low-dose dexamethasone (XVd) relative to other therapies in previously treated MM. Methods : Ovid was systematically searched for phase 2-3 randomized clinical trials (RCTs) in MM that assessed progression-free survival (PFS), overall survival (OS) and overall response rates (ORR). Two population subsets were assessed: second-line patients (2L) and third-line or greater patients (3L+). Base case results compared all regimens against twice weekly bortezomib and dexamethasone (Vd) as the anchored comparator regimen. Results: Forty-seven RCTs met inclusion. For 2L PFS, OS and ORR, XVd had, on average, out of all iterations, the 6th (out of 21), 4th (out of 15), and 5th (out of 20) best result, respectively, versus Vd. For 3L+ PFS, OS and ORR, XVd had the 12th (out of 24), 11th (out of 22), and 8th (out of 25) best result, respectively, versus Vd. There was no statistically significant difference between XVd and other top-ranking therapies for PFS, OS, and ORR in either 2L and 3L+ except for daratumumab/bortezomib/dexamethasone [DVd], which was favorable versus XVd (2L PFS only). Discussion: Results for XVd were more favorable in 2L, having a higher probability of being a top 5 regimen, compared with 3L+ therapies based on the reported clinical trial results. However, in typical clinical practice, most triplet regimens have been modified using weekly bortezomib dosing, raising questions about the actual efficacy of these regimens versus the reported results using twice weekly bortezomib dosing. Conclusions: The addition of XVd, which was designed with once weekly bortezomib dosing, to the treatment landscape for previously treated MM provides a regimen that may potentially be noninferior to the other top 5 regimens in both 2L and 3L+ settings and is associated with less peripheral neuropathy.

Selinexor: Targeting a novel pathway in multiple myeloma

“…A trend toward an OS benefit was also seen (HR 0.84) at the primary analysis, but this did not reach statistical significance. Of note, these benefits were achieved with a lower dose-intensity of bortezomib being used in the selinexor-Vd arm during the first 24 weeks (eight cycles) of treatment [61], perhaps due to reduced toxicity; per the regimen determined in STOMP, patients Based on BOSTON data, a network meta-analysis conducted using Vd as the anchored comparator regimen suggested promising relative efficacy of selinexor-Vd against other options in terms of PFS and OS in the settings of 2nd-line and ≥3rd-line therapy [74], and health economics modelling indicated a manageable budget impact [75] and cost-effectiveness [76] similar to other regimens for RRMM with selinexor-Vd in the early-relapse setting.…”

“…Of note, these benefits were achieved with a lower dose‐intensity of bortezomib being used in the selinexor‐Vd arm during the first 24 weeks (eight cycles) of treatment [61], perhaps due to reduced toxicity; per the regimen determined in STOMP, patients in the selinexor‐Vd arm received bortezomib 1.3 mg/m 2 once‐weekly for 4 weeks in 5‐week cycles, whereas in the Vd arm bortezomib 1.3 mg/m 2 was administered twice‐weekly for 2 weeks in 3‐week cycles. Based on BOSTON data, a network meta‐analysis conducted using Vd as the anchored comparator regimen suggested promising relative efficacy of selinexor‐Vd against other options in terms of PFS and OS in the settings of 2nd‐line and ≥3rd‐line therapy [74], and health economics modelling indicated a manageable budget impact [75] and cost‐effectiveness [76] similar to other regimens for RRMM with selinexor‐Vd in the early‐relapse setting.…”