{
  "abstract": "BACKGROUND: Combined checkpoint blockade (CCB) of programmed-death–1 (PD-1) and cytotoxic-T-lymphocyte–associated protein-4 (CTLA-4) is highly active in melanoma but limited by significant morbidity from immune-related adverse events (irAEs). Effective strategies to prevent CCB-mediated irAEs are lacking.\n\nMETHODS: Patients with advanced melanoma were randomly assigned to receive standard of care ipilimumab and nivolumab alone (Arm A: ipi/nivo, n = 7) or with one cycle of rituximab (Arm B; ipi/nivo+rituximab, n = 7).\n\nRESULTS: Patients receiving ipi/nivo+rituximab experienced lower rates of greater than grade-3(G3) irAEs (14% versus 57%) and superior G3-irAE–free survival compared with those in ipi/nivo arm (2-year G3-irAE-free survival 86% versus 29%, P = 0.01), without adverse impact on tumor regression or survival. G3 hypersensitivity reactions to rituximab (43% in Arm B) prompted trial closure. Rituximab depleted pretherapy activated naive B cells linked to autoimmunity and enhanced CCB-mediated induction of myeloid inflammation and CXCL13+ICOS+ CD4 T cells.\n\nCONCLUSION: B cell depletion favorably modulates CCB-mediated immune activation and may reduce irAE risk.\n\nTRIAL REGISTRATION: ClinicalTrials.gov NCT03719131.\n\nFUNDING: NIH CA238471, AR077926, CA289978, and CA290302.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, Washington, USA.",
    "Seattle Children’s Hospital, Seattle, Washington, USA.",
    "Winship Cancer Institute, Emory University, Atlanta, Georgia, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kavita M. Dhodapkar"
    },
    {
      "affs": [
        0
      ],
      "name": "Antonio Matera"
    },
    {
      "affs": [
        2
      ],
      "name": "Alyssa M. Duffy",
      "orcid": "0000-0003-2848-8661"
    },
    {
      "affs": [
        0
      ],
      "name": "Azmain Taz"
    },
    {
      "affs": [
        2
      ],
      "name": "Renee Julia Manalo"
    },
    {
      "affs": [
        2
      ],
      "name": "Melinda Yushak"
    },
    {
      "affs": [
        2
      ],
      "name": "Ragini Kudchadkar"
    },
    {
      "affs": [
        2
      ],
      "name": "David H. Lawson"
    },
    {
      "affs": [
        0
      ],
      "name": "Madhav V. Dhodapkar"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7df391hp3mmtf.bib",
  "cited_by": 2,
  "doi": "10.1172/jci205606",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722380/",
  "id": "7df391hp3mmtf",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://doi.org/10.1172/jci205606",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Clinical Research and Public Health"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7204210917",
  "pdf_url": "http://www.jci.org/articles/view/205606/files/pdf",
  "pmcid": "PMC13722380",
  "pmid": "42640721",
  "published": "2026-08-25",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/7df391hp3mmtf.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:22:54Z",
      "native_id": "PMC13722380",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci205606"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "B cell depletion improves therapeutic index of combination checkpoint blockade in patients with advanced melanoma",
  "title_text": "B cell depletion improves therapeutic index of combination checkpoint blockade in patients with advanced melanoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:54Z",
  "url": "https://research.draconitic.com/paper/7df391hp3mmtf",
  "venue": "The Journal of Clinical Investigation",
  "versions": []
}