A comparison of the efficacy of immunomodulatory-free regimens in relapsed or refractory multiple myeloma: a network meta-analysis

Weisel, Katja; Sonneveld, Pieter; Spencer, Andrew; Beksaç, Meral; Rizzo, Maria Teresa; Xu, Ying; Fahrbach, Kyle; Gaudig, Maren; Slavcev, Mary; Dearden, Lindsay; Lam, Annette

doi:10.1080/10428194.2018.1466392

Cited by 9 publications

(8 citation statements)

References 17 publications

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“…While the 2L studies had a slightly longer mean follow-up time than the 3L+ studies (26.3 months versus 22.7 months, respectively), other baseline characteristics were generally similar between the 2 groups (mean age 64.2 years versus 64.6 years, 56.4% male versus 55.2% male), which could suggest that the resulting differences between 2L and 3L+ studies may be due to exposure to prior lines of therapy, given that the characteristics of previous therapy can have major influences on the treatment effect of later interventions. 32 Differences in these studies may also be attributed to the proportion of elderly/frail populations and/or patients with high-risk cytogenetics. In the BOSTON trial, more than half of patients in the XVd arm (50.5%) and 48.5% in the Vd arm reported high-risk cytogenetics.…”

Section: Discussionmentioning

confidence: 99%

“…Results from our study align with previous findings in NMAs with previously treated MM. 32 32 A more recent NMA by Arcuri et al, reviewed phase 3 trials with control arms that included lenalidomide or bortezomib (considering them equivalent therapies) and similarly found the compared therapies (daratumumab, pegylated liposomal doxorubicin, isatuximab, carfilzomib, pomalidomide, panobinostat, venetoclax, ixazomib, XVd, elotuzumab, cyclophosphamide, vorinostat, high-dose chemotherapy, ld, and Vd) to be similar in PFS and OS, with the exception of daratumumab triplet regimens, which performed significantly better. 35 Selinexor triplet combinations including XDd and XPd are recommended on the NCCN Guidelines for previously treated MM.…”

Section: Discussionmentioning

confidence: 99%

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

Dolph¹,

Tremblay²,

Gilligan

et al. 2021

Journal of Health Economics and Outcomes Research

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Dolph¹,

Tremblay²,

Gilligan

et al. 2021

Journal of Health Economics and Outcomes Research

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“…Synthesis of evidence of RCTs in RRMM has been described previously . Using all phase 3 RCTs and a fixed‐effect Bayesian method, van Beurden‐Tan et al performed an NMA of 17 RCTs for 16 different combinations with PFS as the primary endpoint for efficacy.…”

Section: Discussionmentioning

confidence: 99%

Association of adverse events and associated cost with efficacy for approved relapsed and/or refractory multiple myeloma regimens: A Bayesian network meta‐analysis of phase 3 randomized controlled trials

Dhakal

Narra

Giri

et al. 2020

Cancer

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BACKGROUND: Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs). METHODS: Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs). RESULTS: Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). CONCLUSIONS: The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM.

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“…Many of these limitations exist and were noted in other NMAs of previously treated MM. 32,[35][36][37]…”

Section: Limitationsmentioning

confidence: 99%

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

Dolph¹,

Tremblay²,

Gilligan

et al. 2021

JHEOR

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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.

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A comparison of the efficacy of immunomodulatory-free regimens in relapsed or refractory multiple myeloma: a network meta-analysis

Cited by 9 publications

References 17 publications

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

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

Association of adverse events and associated cost with efficacy for approved relapsed and/or refractory multiple myeloma regimens: A Bayesian network meta‐analysis of phase 3 randomized controlled trials

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

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