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Development of anti-drug antibodies is associated with shortened survival in patients with metastatic melanoma treated with ipilimumab

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  1. Neo-antigen specific memory T-cell responses in healthy individuals

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  2. Immunoprofiles of colorectal cancer from Lynch syndrome

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  3. Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study

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  4. Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model

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  5. Frequent adaptive immune responses against arginase-1

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  1. Peripheral memory T cells specific for Arginase-1

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  2. Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells

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  3. Real-world evidence to guide healthcare policies in oncology

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  4. undersøges !!

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Introduction: Checkpoint inhibitors, including the CTLA-4 blocking antibody ipilimumab, have become the new standard therapy for many metastatic cancers. Development of anti-drug antibodies (ADAs) after treatment with other biopharmaceuticals has been thoroughly described, but the induction of ADAs after treatment with checkpoint inhibitors has been inadequately investigated. In this retrospective study, we relate ipilimumab serum levels and anti-ipilimumab antibody levels to clinical outcomes in patients with metastatic melanoma (MM). Method: Serum samples from 31 patients with MM were analyzed for serum levels of ipilimumab and ADAs to ipilimumab at baseline, and before the 2nd and 4th infusion using an in-house bead-based assay. The results were correlated with progression-free survival (PFS) and overall survival (OS). Results: Low serum levels of ipilimumab before the 2nd infusion correlated significantly with a shorter OS (p = 0.01) and PFS (p = 0.02). Eight patients (26%) were ADA-positive at either timepoint. ADA positivity correlated significantly with a shorter OS (p = 0.03) with a hazard ratio (HR) of 3.0 (95% CI: 1.2-7.8). Four of 8 ADA-positive patients (50%) discontinued therapy before the 4th infusion due to disease progression, compared to three of 23 (13%) ADA-negative patients. Conclusion: We confirm that low serum levels of ipilimumab are associated with a shortened OS, and we show for the first time that ADAs to ipilimumab are associated with shorter OS in patients with MM.

Original languageEnglish
JournalOncoImmunology
Volume7
Issue number5
Pages (from-to)e1424674
ISSN2162-4011
DOIs
Publication statusPublished - 2018

ID: 54806103