A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation

Weisel, Katja; Doyen, Chantal; Dimopoulos, Meletios Α.; Yee, Adrian; Lahuerta, Juan José; Martin, Amber; Travers, Karin; Druyts, Eric; Toor, Kabirraaj; Abildgaard, Niels; Lu, Jin; Droogenbroeck, Jan Van; Geraldes, Catarina; Petrini, Mario; Voillat, Laurent; Voog, Éric; Façon, Thierry

doi:10.1080/10428194.2016.1177772

Cited by 32 publications

(31 citation statements)

References 39 publications

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“…Several NMAs have been published in the last decade . A recent one by Weisel et al included different treatment guidelines to avoid possible biases. However, the primary analysis included both studies of non‐candidate population for transplant without age restriction and other trials that restricted the use of treatment to very advanced ages .…”

Section: Discussionmentioning

confidence: 99%

“…Not‐blinded clinical trials can be influenced by investigators and promoters, especially for outcomes with a margin of subjectivity such as PFS. Moreover, the lack of homogeneity of treatment schedules in nodes could translate into greater uncertainty of results, as has been seen in other first‐line NMAs for MM treatment in patients who are not transplant candidates . It is also necessary to consider the influence of different patient profiles on this indication according to several characteristics (age, staging, cytogenetic pattern, etc).…”

Section: Methodsmentioning

confidence: 99%

“…Although NMAs can be a very useful tool, their results should only be taken into consideration if clinical trials with similar characteristics have been selected. A frequent problem of NMAs in the first line of treatment for MM is that they include clinical trials with heterogeneous populations as candidate and non‐candidate patients for stem cell transplantation, or elderly patients (sometimes ≥ 75 years) and the general population. The transplant‐ineligible population includes patients over 65 years of age or with comorbidities that imply that such a risky intervention is not recommended, as seen in the inclusion criteria of clinical trials .…”

Section: Introductionmentioning

confidence: 99%

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Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients

Gil‐Sierra

Gimeno‐Ballester

Fenix-Caballero

et al. 2020

European J of Haematology

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Objectives Multiple myeloma (MM) is a complex disease. Lack of direct comparisons among treatments and incorporation of new alternatives make it necessary to perform studies that allow for clinical decision‐making. A network meta‐analysis (NMA) was developed to evaluate the comparative efficacy among different therapeutic alternatives in newly diagnosed transplant‐ineligible MM patients. Methods MEDLINE® and EMBASE® were systematically searched up for these drugs: lenalidomide, thalidomide, bortezomib, and daratumumab. Comparative phase II‐III randomized clinical trials (RCTs) were included. Progression‐free survival (PFS) was selected as efficacy outcome. The NMA was developed using Bayesian methods. Fixed‐ and random‐effects models were assessed using deviance information criteria. Results The systematic search yielded 593 results. Ten RCTs were included. No differences were observed between fixed‐ and random‐effects models. The combination of daratumumab, bortezomib, melphalan, and prednisone showed the best HR in PFS (reference treatment). Along with this scheme, the best PFS results were obtained by combination of daratumumab, lenalidomide, and dexamethasone (HR 1.2, 95% CrI 0.64‐2.4) and bortezomib with lenalidomide and dexamethasone (HR 1.6, 95% CrI 0.81‐3.0). Conclusions Schemes with the best PFS results were daratumumab treatments and combination of bortezomib, lenalidomide, and dexamethasone, although the latter scheme has been analyzed in heterogeneous populations.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients

Gil‐Sierra

Gimeno‐Ballester

Fenix-Caballero

et al. 2020

European J of Haematology

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“…Not all patients are eligible for triple therapy during subsequent lines of treatment; this is especially relevant in the context of an increasingly elderly population. Although there are no direct, randomised data comparing Rd and VMP, lenalidomide is expected to be more effective than current first-line therapies, as suggested by the FIRST trial results and supported by the indirect comparison of treatments conducted by Weisel et al [5–7]. Using lenalidomide, therefore, delays the time to subsequent therapy because of its improvement in time to progression compared to other first-line therapies, but we are aware that the duration of treatment may vary across countries, which may further affect treatment efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Further analysis showed that median OS was 58.9, 56.7, and 48.5 months for patients treated with continuous lenalidomide–dexamethasone, 18 cycles of lenalidomide–dexamethasone, and MPT, respectively; for continuous lenalidomide–dexamethasone, this represents a 10.4-month improvement in OS compared with those receiving MPT [6]. The increased survival benefit with lenalidomide was confirmed by Weisel et al, who conducted a network meta-analysis of survival in randomised controlled myeloma trials; lenalidomide was associated with a significant progression-free and overall survival advantage versus other first-line treatments (bortezomib, melphalan, and prednisone [VMP] and MPT) [7]. In addition to its favourable efficacy and acceptable toxicity profile, lenalidomide is an oral therapy requiring fewer hospital visits for treatment administration compared with alternative subcutaneous or intravenous agents [8–10], making this a more acceptable and better tolerated class of drugs.…”

Section: Introductionmentioning

confidence: 99%

The Cost Impact of Lenalidomide for Newly Diagnosed Multiple Myeloma in the EU5

et al. 2017

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IntroductionLenalidomide is an active agent that was approved for use in the EU in 2015 as a first-line therapy for previously untreated, non-transplant eligible multiple myeloma patients. Our objective was to assess the cost impact of lenalidomide when selected as a first-line treatment for transplant-ineligible patients in France, Germany, Italy, Spain, and the United Kingdom (EU5).MethodsWe developed a cost-impact model of the total costs associated with newly diagnosed multiple myeloma over 5 years in the EU5 based on treatment duration and time to progression (TTP) (taken from trial data). We compared a baseline scenario (of current lenalidomide uptake) with two alternative future scenarios. Future Scenario A used an increased uptake of first-line lenalidomide: up to 50% in Year 5. Future Scenario B was similar to the baseline, but included a 20% increased uptake of the triple therapy regimen, carfilzomib, lenalidomide, and dexamethasone (KRd) at second line.ResultsCompared to alternative first-line care pathways, lenalidomide provides a time to progression advantage of up to 5.1 months. In the baseline scenario, the costs per patient were €40,692 in Year 1. Future Scenario A showed an additional expenditure of €867 per patient in Year 1, increasing to €3358 per patient by Year 5, a 2.1% and 8.2% increase from baseline, respectively. However, lenalidomide use was associated with a lower monthly hospitalisation per-patient cost (€813) compared with bortezomib (€1173) and thalidomide (€1532). Future Scenario B was associated with a 29% increase in cost.ConclusionsCompared to other first line therapies, lenalidomide delays time to progression resulting in associated savings across a patient’s treatment pathway and overall is likely to result in a limited impact on budget. Lenalidomide should, therefore, be considered as a first treatment option for multiple myeloma patients ineligible for transplant.FundingCelgene Ltd.

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