{
  "abstract": "Multiple myeloma (MM) outcomes have improved with proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and transplantation, yet a subset of patients with high-risk MM (HRMM) continues to relapse early and die prematurely. Immune effector therapies (IET)—B-cell maturation antigen (BCMA)- and G protein–coupled receptor class C group 5 member D (GPRC5D)-directed chimeric antigen receptor T cells (CAR-T) and bispecific antibodies—have transformed the treatment of relapsed/refractory MM. However, their benefit in HRMM remains incompletely defined. This review describes how HRMM is defined in the IET-era distinguishing baseline biological/genomic risk, clinical high-risk phenotypes, and IET-specific adverse predictors. The International Myeloma Society/International Myeloma Working Group consensus integrates adverse cytogenetics and beta-2 microglobulin, whereas functional high-risk disease, extramedullary disease (EMD), plasma cell leukemia (PCL), high tumor burden, inflammation, and prior BCMA exposure identify aggressive disease in relapsed patients. Across pivotal trials, CAR-T therapy, particularly ciltacabtagene autoleucel, and selected bispecific antibodies retain activity in high-risk cytogenetic subgroups, whereas EMD and PCL remain associated with inferior responses and short progression-free survival. Emerging dual-antigen and trispecific engagers, along with novel targets such as FcRH5 and CD70, aim to overcome antigen escape. Prospective, biology-informed studies are needed to achieve durable disease control in HRMM.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Hematology, Department of Medicine, Mayo Clinic , , ,",
    "Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute , , ,"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yoshito Nishimura"
    },
    {
      "affs": [
        0
      ],
      "name": "Gunjan Gaur"
    },
    {
      "affs": [
        1
      ],
      "name": "Francesca Cottini"
    },
    {
      "affs": [
        0
      ],
      "name": "Saurabh Zanwar"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b3p8q6rntbvxd.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1956522",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669832/?tool=EBI",
  "id": "b3p8q6rntbvxd",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13669832",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Multiple Myeloma Research and Treatments"
    ]
  ],
  "openalex": "W7215119767",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669832/pdf/?tool=EBI",
  "pmcid": "PMC13669832",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/b3p8q6rntbvxd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13669832",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13669832"
    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1956522",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1956522/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "Reshaping the definition of high-risk disease in the immune effector therapy era in multiple myeloma",
  "title_text": "Reshaping the definition of high-risk disease in the immune effector therapy era in multiple myeloma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/b3p8q6rntbvxd",
  "venue": "Frontiers in oncology",
  "versions": []
}