Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis

Blommestein, Hedwig M.; Beurden-Tan, Chrissy H. Y. Van; Franken, M; Groot, Carin A. Uyl–de; Sonneveld, Pieter

doi:10.3324/haematol.2018.206912

Cited by 21 publications

(23 citation statements)

References 53 publications

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“…In the intent-to-treat sensitivity analysis, the difference in PFS between FH patients treated with VRd and Rd was smaller in magnitude, which likely reflects higher rates of treatment discontinuation among patients treated with VRd in routine clinical practice ( Figure S2 in Appendix S1). 21 which is consistent with our finding of no statistically significant differences between Vd and Rd in FH.…”

Section: Primary Outcome: Progression-free Survivalsupporting

confidence: 93%

Daratumumab‐lenalidomide‐dexamethasone vs standard‐of‐care regimens: Efficacy in transplant‐ineligible untreated myeloma

et al. 2020

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Daratumumab in combination with lenalidomide-dexamethasone (D-Rd) recently received FDA approval for the treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression-free survival (PFS) in patients treated with D-Rd in the MAIA trial and patients treated with common standard-of-care regimens from the Flatiron Health electronic health record-derived deidentified database, which has data from patients treated primarily at community-based oncology practices in the United States. Individual-level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D-Rd to bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-dexamethasone (Vd); lenalidomide-dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D-Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D-Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity-score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D-Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D-Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head-to-head trials comparing D-Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant-ineligible patients with NDMM. 1 | INTRODUCTION Daratumumab in combination with lenalidomide-dexamethasone (D-Rd) received approval from the US Food and Drug Administration (FDA) in June 2019 for the treatment of patients with newly diagnosed multiple myeloma (NDMM) who were ineligible for autologous stem cell transplant (ASCT). 1 FDA approval was based on results from a prespecified interim analysis of data from the MAIA phase III clinical trial, which showed that D-Rd was associated with a significantly lower risk of disease progression or death relative to lenalidomide-dexamethasone

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Section: Primary Outcome: Progression-free Survivalsupporting

confidence: 93%

Daratumumab‐lenalidomide‐dexamethasone vs standard‐of‐care regimens: Efficacy in transplant‐ineligible untreated myeloma

et al. 2020

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“…Our network also discriminates between MPT and MPT‐T and does not mix populations, reducing the amount of bias. In addition, Blommestein et al did not analyze the Da_RD_Da combination . The most recent NMA by Cao et al contains all available combinations, including daratumumab treatments .…”

Section: Discussionmentioning

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%

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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“…An NMA comparing Rd with regimens investigated in RCTs that included patients with NDMM who were aged >65 years reported improved outcomes for response rate, OS, and PFS for Rd, however RVd, VMP + D, and D þ Rd were not included in this analysis [48]. A recently published NMA of treatments for patients with TNE NDMM [49] used a random-effects model with a wide evidence network similar to our extended network. However, their conclusions differ slightly from ours; the relative ordering of VMP þ D and RVd in terms of PFS impact is reversed, with VMP þ D ranked ahead of RVd.…”

Section: Sensitivity Analysesmentioning

confidence: 99%

Relative efficacy of treatment options in transplant-ineligible newly diagnosed multiple myeloma: results from a systematic literature review and network meta-analysis

Ramasamy

Dhanasiri

Thom

et al. 2019

Leukemia & Lymphoma

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Established treatments for transplant-ineligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) include melphalan and prednisone (MP) combined with either bortezomib (VMP) or thalidomide (MPT), or lenalidomide plus low-dose dexamethasone (Rd). New treatments for TNE NDMM include Rd plus bortezomib (RVd) and daratumumab plus VMP (VMP þ D), daratumumab plus lenalidomide and dexamethasone (D þ Rd). Relative efficacy of these treatments was compared using a network meta-analysis. Eight trials identified by a systematic literature review were included in the primary analysis; hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were used. Rd was superior to other MP-based regimens for OS and PFS. There was strong evidence that, compared with Rd, both D þ Rd and RVd improved PFS (HR 0.57; 95% credible interval (CrI) 0.43, 0.73 and HR 0.72; 95% CrI 0.56, 0.91, respectively). However, there was strong evidence only for RVd in respect to OS (HR 0.72; 95% CrI 0.52, 0.96).

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Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis

Cited by 21 publications

References 53 publications

Daratumumab‐lenalidomide‐dexamethasone vs standard‐of‐care regimens: Efficacy in transplant‐ineligible untreated myeloma

Daratumumab‐lenalidomide‐dexamethasone vs standard‐of‐care regimens: Efficacy in transplant‐ineligible untreated myeloma

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

Relative efficacy of treatment options in transplant-ineligible newly diagnosed multiple myeloma: results from a systematic literature review and network meta-analysis

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