{
  "abstract": "Daratumumab-lenalidomide (DR) combination therapy improves multiple myeloma (MM) outcomes, yet some patients respond poorly. We examined 21 DR pre-treatment samples from the IFM2017-03 phase 3 trial using single-cell and bulk multiomics approaches to identify determinants of response. Analysis of the bone marrow environment revealed a coordinated inflammatory state across immune and myeloma cells associated with DR resistance. We identified upregulated NF-κB signaling genes in monocytes of non-responders, alongside increased proinflammatory ISG + T cells and attenuated NK cell CD16 expression, suggesting an impairment of antibody-dependent cellular cytotoxicity essential for daratumumab efficacy. Concurrently, myeloma cells displayed enhanced NF-κB activation, supporting convergent tumor and immune inflammatory programs. We further developed an eight-gene NF-κB-related signature that robustly predicted treatment response in independent bone marrow (n = 28, AUC = 0.81) and peripheral blood (n = 40, AUC = 0.77) samples. Our study underscores an NF-κB-associated inflammatory axis underlying poor DR response and suggests that targeting inflammatory pathways a potential therapeutic avenue warranting further investigation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "Wenwen Cheng"
    },
    {
      "name": "Silvia Gaggero"
    },
    {
      "name": "Lama Hasan Bou Issa"
    },
    {
      "name": "Aïcha Ouelkdite"
    },
    {
      "name": "Guillaume Escure"
    },
    {
      "name": "Adeline Cozzani"
    },
    {
      "name": "Yanick Njosse Tchantchou"
    },
    {
      "name": "Noémie Carlier"
    },
    {
      "name": "Emilie Wauquier"
    },
    {
      "name": "Gauthier Decool"
    },
    {
      "name": "Rémi Tilmont"
    },
    {
      "name": "Benjamin Podvin"
    },
    {
      "name": "Malo Leprohon"
    },
    {
      "name": "Mojtaba Shekarkar"
    },
    {
      "name": "Léa Fléchon"
    },
    {
      "name": "Angélina Kasprowicz"
    },
    {
      "name": "Sophie Groux-Degroote"
    },
    {
      "name": "Jérôme Moreaux"
    },
    {
      "name": "Bertrand Arnulf"
    },
    {
      "name": "Jill Corre"
    },
    {
      "name": "Céline Villenet"
    },
    {
      "name": "Ludovic Martinet"
    },
    {
      "name": "Xavier Leleu"
    },
    {
      "name": "Martin Figeac"
    },
    {
      "name": "Thierry Facon"
    },
    {
      "name": "Wenfei Jin"
    },
    {
      "name": "Suman Mitra"
    },
    {
      "name": "Salomon Manier"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/38trdjdzkqzsr.bib",
  "cited_by": 0,
  "doi": "10.1186/s40364-026-00992-2",
  "fulltext_url": null,
  "id": "38trdjdzkqzsr",
  "issns": [
    "2050-7771"
  ],
  "landing_url": "https://hal.science/hal-05745245v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2720|Multiple Myeloma Research and Treatments"
    ]
  ],
  "openalex": "W7208832643",
  "pdf_url": "https://link.springer.com/content/pdf/10.1186/s40364-026-00992-2.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-05",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/38trdjdzkqzsr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:33Z",
      "native_id": "hal-05745245",
      "source": "hal",
      "url": "https://hal.science/hal-05745245v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    }
  ],
  "title": "Inflammatory bone marrow microenvironment impairs the therapeutic effect of daratumumab-lenalidomide in multiple myeloma",
  "title_text": "Inflammatory bone marrow microenvironment impairs the therapeutic effect of daratumumab-lenalidomide in multiple myeloma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:33Z",
  "url": "https://research.draconitic.com/paper/38trdjdzkqzsr",
  "venue": "Biomarker Research",
  "versions": []
}