Evidence map›Paper›PMID 41353340›Full record

SynthesisBlood cancer journal2025

Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis.

João Tadeu Damian Souto Filho, Lucas Oliveira Cantadori, Edvan de Queiroz Crusoe, Vania Hungria, Angelo Maiolino

Abstract readMeta-AnalysisNetwork Meta-AnalysisSystematic Review
In one paragraph

Synthesis in Blood cancer journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
–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

3 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
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

5 authors.

João Tadeu Damian Souto FilhoFaculdade de Medicina de Campos, Campos dos Goytacazes, Rio de Janeiro, Brazil. drjoaotadeu@yahoo.com.br.ORCID 0000-0003-2641-1425
Lucas Oliveira CantadoriHospital das Clínicas, Universidade Estadual Paulista, UNESP, Botucatu, São Paulo, Brazil.
Edvan de Queiroz CrusoeUniversidade Federal da Bahia, Salvador, Bahia, Brazil.ORCID 0000-0002-8599-4731
Vania Hungria *Clínica São Germano, São Paulo, Brazil.ORCID 0000-0002-4327-1957
Angelo Maiolino *Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.ORCID 0000-0003-0140-9548

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Frontline therapy for transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) has advanced with anti-CD38 monoclonal antibody (mAb)-based regimens. Although quadruplet combinations incorporating daratumumab and isatuximab have demonstrated improved response rates and progression-free survival (PFS), comparative overall survival (OS) data remain limited. We performed a systematic review, network meta-analysis (NMA), and reconstructed individual patient data meta-analysis comparing survival outcomes of quadruplet versus triplet regimens in TI-NDMM. This study adhered to Cochrane and PRISMA guidelines and was registered prospectively (PROSPERO CRD420251033401). A comprehensive literature search through April 2025 identified randomized clinical trials (RCT) evaluating quadruplet and triplet regimens involving daratumumab, isatuximab, bortezomib, lenalidomide, and dexamethasone in any combination, compared to their backbone regimens, reporting OS and PFS. Four RCT (n = 2,038) were included. At 60 months, estimated PFS rates were: D-VRd (66.4%), I-VRd (63.2%), D-Rd (51.9%), and VRd (42.6%). Both D-VRd and I-VRd significantly improved PFS compared with D-Rd (HR 0.65; 95% CI 0.48-0.87; and HR 0.68; 95% CI 0.52-0.89) and VRd (HR 0.51; 95% CI 0.39-0.67; and HR 0.53; 95% CI 0.41-0.67). D-Rd also showed superior PFS over VRd (HR 0.77, 95% CI 0.64-0.93; P = 0.007). At 60 months, OS rates were: D-VRd (72.8%), I-VRd (72.2%), D-Rd (67.1%), and VRd (67.0%). Pooled analyses demonstrated that quadruplets significantly improved both PFS (64.7% vs. 46.3%; HR 0.57, 95% CI 0.47-0.69; P < 0.0001) and OS (72.5% vs. 67.1%; HR 0.78, 95% CI 0.63-0.96; P = 0.02) compared to triplet regimens. The OS benefit of quadruplets was consistent in comparisons against both D-Rd (HR 0.77; 95% CI: 0.60-0.98; P = 0.04) and VRd (HR 0.77; 95% CI: 0.62-0.97; P = 0.02). In the NMA, quadruplet regimens ranked highest for complete response, PFS, and OS. This meta-analysis supports anti-CD38 mAb-based quadruplet regimens as superior frontline therapy in TI-NDMM, significantly improving overall survival.

Indexed as

ADP-ribosyl Cyclase 1Antineoplastic Combined Chemotherapy ProtocolsMultiple MyelomaAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBortezomibDexamethasoneHumansLenalidomideMembrane GlycoproteinsADP-ribosyl Cyclase 1Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedBortezomibCD38 protein, humandaratumumabDexamethasoneisatuximabLenalidomideMembrane Glycoproteins

Identifiers

PMID41353340
PMCPMC12681503

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.