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Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma.
Gonzalez-Kozlova, Edgar; Huang, Hsin-Hui; Jagede, Opeyemi A; Tuballes, Kevin; Del Valle, Diane M; Kelly, Geoffrey; Patel, Manishkumar; Xie, Hui; Harris, Jocelyn; Argueta, Kimberly; Nie, Kai; Barcessat, Vanessa; Moravec, Radim; Altreuter, Jennifer; Duose, Dzifa Y; Kahl, Brad S; Ansell, Stephen M; Yu, Joyce; Cerami, Ethan; Lindsay, James R; Wistuba, Ignacio I; Kim-Schulze, Seunghee; Diefenbach, Catherine S; Gnjatic, Sacha.
Afiliación
  • Gonzalez-Kozlova E; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Huang HH; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Jagede OA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Tuballes K; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Del Valle DM; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Kelly G; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Patel M; Department of Oncological Sciences, 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; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Moravec R; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Altreuter J; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Duose DY; Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, NCI, Bethesda, Maryland.
  • Kahl BS; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Ansell SM; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Yu J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Cerami E; Washington University School of Medicine, New York, New York.
  • Lindsay JR; Mayo Clinic, New York, New York.
  • Wistuba II; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Kim-Schulze S; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Diefenbach CS; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Gnjatic S; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer Res Commun ; 4(7): 1726-1737, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38934093
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Hodgkin / Protocolos de Quimioterapia Combinada Antineoplásica / Resistencia a Antineoplásicos / Ipilimumab / Nivolumab / Brentuximab Vedotina Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Hodgkin / Protocolos de Quimioterapia Combinada Antineoplásica / Resistencia a Antineoplásicos / Ipilimumab / Nivolumab / Brentuximab Vedotina Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos