Evidence map›Paper›PMID 40669094›Full record

SynthesisESMO open2025

A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients.

E A Martino, G Caridà, D Lofaro, A Bruzzese, C Labanca, F Mendicino, E Lucia, V Olivito, N Puccio, A Neri and 4 more

Abstract readNetwork Meta-AnalysisSystematic Review
In one paragraph

Synthesis in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

E A MartinoHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
G CaridàHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy; Department of Experimental and Clinical Medicine, University of Catanzaro, Catanzaro, Italy.
D LofaroDepartment of Mathematics and Computer Science, University of Calabria, Rende, Italy.
A BruzzeseHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
C LabancaHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
F MendicinoHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
E LuciaHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
V OlivitoHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
N PuccioLaboratory of Translational Research Azienda USL-IRCSS di Reggio Emilia, Reggio Emilia, Italy.
A NeriScientific Directorate, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. Electronic address: antonino.neri@ausl.re.it.
N AmodioDepartment of Experimental and Clinical Medicine, University of Catanzaro, Catanzaro, Italy.
E VignaHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy. Electronic address: ernesto.vigna@aocs.it.
F MorabitoGruppo Amici Dell'Ematologia Foundation-GrADE, Reggio Emilia, Italy.
M GentileHematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy; Department of Pharmacy, Health and Nutritional Science, University of Calabria, Rende, Italy. Electronic address: massimo.gentile@unical.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe treatment landscape for relapsed/refractory multiple myeloma (RRMM) is rapidly evolving, particularly for patients exposed or refractory to lenalidomide. With the aim of evaluating the relative efficacy of lenalidomide-free regimens as second-line treatment options, an updated network meta-analysis, incorporating phase II/III randomized controlled trials, has been conducted. MATERIALS AND

methodsA systematic literature search identified eight eligible trials comprising 3952 patients. The primary outcome was progression-free survival (PFS), analyzed through Bayesian and frequentist approaches.

resultsOur findings indicate that belantamab mafodotin, bortezomib, and dexamethasone (BVd) combination is the most effective regimen for both lenalidomide-exposed and lenalidomide-refractory MM patients at first relapse, achieving the highest surface under the cumulative ranking curve for PFS. BVd outperformed other triplet regimens, including daratumumab, bortezomib, and dexamethasone, isatuximab, carfilzomib, and dexamethasone, and bortezomib, pomalidomide, and dexamethasone.

conclusionsEmerging therapies, including chimeric antigen receptor T-cell (CAR-T-cell) therapy and bispecific antibodies, are set to reshape RRMM treatment paradigms. Trials such as CARTITUDE-4 and MajesTEC-3 are exploring these agents in earlier treatment lines, particularly for lenalidomide- and daratumumab-refractory patients. Our analysis provides an evidence-based hierarchy of lenalidomide-free regimens, supporting BVd as a preferred second-line treatment. Future studies should refine treatment sequencing strategies and evaluate novel agents in earlier disease stages to optimize outcomes for RRMM patients.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsLenalidomideMultiple MyelomaBortezomibDexamethasoneHumansProgression-Free SurvivalRandomized Controlled Trials as TopicBortezomibDexamethasoneLenalidomidelenalidomide refractorynetwork meta-analysisprogression-free survivalrelapsed/refractory multiple myelomatriplet regimens

Identifiers

PMID40669094
PMCPMC12281279

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.