دورية أكاديمية
أعرض في EDS

Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma.

التفاصيل البيبلوغرافية
العنوان: Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma.
المؤلفون: Gonzalez-Kozlova E; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Huang HH; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York., Jagede OA; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Tuballes K; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Del Valle DM; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Kelly G; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Patel M; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Xie H; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Harris J; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Argueta K; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Nie K; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Barcessat V; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Moravec R; Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, NCI, Bethesda, Maryland., Altreuter J; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Duose DY; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kahl BS; Washington University School of Medicine, New York, New York., Ansell SM; Mayo Clinic, New York, New York., Yu J; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Cerami E; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Lindsay JR; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Wistuba II; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kim-Schulze S; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York., Diefenbach CS; Perlmutter Cancer Center, NYU Langone Health, New York, New York., Gnjatic S; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
المصدر: Cancer research communications [Cancer Res Commun] 2024 Jul 01; Vol. 4 (7), pp. 1726-1737.
نوع المنشور: Journal Article; Clinical Trial, Phase II; Multicenter Study; Clinical Trial, Phase I
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]-
مواضيع طبية MeSH: Brentuximab Vedotin*/therapeutic use , Hodgkin Disease*/drug therapy , Hodgkin Disease*/immunology , Hodgkin Disease*/blood , Nivolumab*/therapeutic use , Nivolumab*/administration & dosage , Ipilimumab*/therapeutic use , Ipilimumab*/administration & dosage , Ipilimumab*/pharmacology , Drug Resistance, Neoplasm* , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use, Humans ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult
مستخلص: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy.
Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL.
(©2024 The Authors; Published by the American Association for Cancer Research.)
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معلومات مُعتمدة: U24 CA224319 United States CA NCI NIH HHS; U01 DK124165 United States DK NIDDK NIH HHS; U24 CA224316 United States CA NCI NIH HHS; U24 CA224331 United States CA NCI NIH HHS; UG1 CA232760 United States CA NCI NIH HHS; U24 CA224285 United States CA NCI NIH HHS; UL1 TR004419 United States TR NCATS NIH HHS; U10 CA180820 United States CA NCI NIH HHS; U10 CA180794 United States CA NCI NIH HHS; P30 CA196521 United States CA NCI NIH HHS; UG1 CA233339 United States CA NCI NIH HHS
المشرفين على المادة: 7XL5ISS668 (Brentuximab Vedotin)
31YO63LBSN (Nivolumab)
0 (Ipilimumab)
تواريخ الأحداث: Date Created: 20240627 Date Completed: 20240715 Latest Revision: 20240717
رمز التحديث: 20240717
مُعرف محوري في PubMed: PMC11247952
DOI: 10.1158/2767-9764.CRC-24-0252
PMID: 38934093
قاعدة البيانات: MEDLINE
الوصف
تدمد:2767-9764
DOI:10.1158/2767-9764.CRC-24-0252