G M Haag1, I Zoernig2, J C Hassel3, N Halama2, J Dick3, N Lang3, L Podola4, J Funk2, C Ziegelmeier2, S Juenger4, M Bucur4, L Umansky4, C S Falk5, A Freitag6, I Karapanagiotou-Schenkel6, P Beckhove7, A Enk3, D Jaeger8. 1. Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Germany. Electronic address: GeorgMartin.Haag@med.uni-heidelberg.de. 2. Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Germany. 3. Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Germany. 4. Translational Immunology, National Center for Tumor Diseases, Heidelberg, Germany. 5. Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany. 6. NCT Trial Center, National Center for Tumor Diseases, Heidelberg, Germany. 7. Translational Immunology, National Center for Tumor Diseases, Heidelberg, Germany; Regensburg Center for Interventional Immunology, University Hospital Regensburg, Germany. 8. Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Germany; Clinical Cooperation Unit "Applied Tumor-Immunity", German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract
BACKGROUND: Immune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1-specific immunity. PATIENTS AND METHODS: Twenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks. Primary endpoint was the disease control rate (irCR, irPR or irSD) according to immune-related response criteria (irRC). Secondary endpoints included the disease control rate according to RECIST criteria, progression-free survival and overall survival (OS). Humoural and cellular immune responses against NY-ESO-1 were analysed from blood samples. RESULTS: Disease control rate according to irRC was 52%, irPR was observed in 36% of patients. Progression-free survival according to irRC was 7.8 months, according to RECIST criteria it was 2.9 months. Median OS was 22.7 months; the corresponding 1-year survival rate was 66.8%. Treatment-related grade 3 AEs occurred in 36% with no grade 4-5 AEs. No clear association was found between the presence of NY-ESO-1-specific cellular or humoural immune responses and clinical activity. CONCLUSION: Ipilimumab demonstrated clinically relevant activity within this biomarker-defined population. NY-ESO-1 positivity, as a surrogate for a preexisting immune response against tumour antigens, might help identifying patients with a superior outcome from immune checkpoint blockade. CLINICAL TRIAL INFORMATION: NCT01216696.
BACKGROUND: Immune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanomapatients with preexisting NY-ESO-1-specific immunity. PATIENTS AND METHODS: Twenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks. Primary endpoint was the disease control rate (irCR, irPR or irSD) according to immune-related response criteria (irRC). Secondary endpoints included the disease control rate according to RECIST criteria, progression-free survival and overall survival (OS). Humoural and cellular immune responses against NY-ESO-1 were analysed from blood samples. RESULTS: Disease control rate according to irRC was 52%, irPR was observed in 36% of patients. Progression-free survival according to irRC was 7.8 months, according to RECIST criteria it was 2.9 months. Median OS was 22.7 months; the corresponding 1-year survival rate was 66.8%. Treatment-related grade 3 AEs occurred in 36% with no grade 4-5 AEs. No clear association was found between the presence of NY-ESO-1-specific cellular or humoural immune responses and clinical activity. CONCLUSION:Ipilimumab demonstrated clinically relevant activity within this biomarker-defined population. NY-ESO-1 positivity, as a surrogate for a preexisting immune response against tumour antigens, might help identifying patients with a superior outcome from immune checkpoint blockade. CLINICAL TRIAL INFORMATION: NCT01216696.
Authors: Mirjam Fässler; Stefan Diem; Joanna Mangana; Omar Hasan Ali; Fiamma Berner; David Bomze; Sandra Ring; Rebekka Niederer; Cristina Del Carmen Gil Cruz; Christian Ivan Pérez Shibayama; Michal Krolik; Marco Siano; Markus Joerger; Mike Recher; Lorenz Risch; Sabine Güsewell; Martin Risch; Daniel E Speiser; Burkhard Ludewig; Mitchell P Levesque; Reinhard Dummer; Lukas Flatz Journal: J Immunother Cancer Date: 2019-02-20 Impact factor: 13.751
Authors: Chloe B Rodgers; Colette J Mustard; Ryan T McLean; Sharon Hutchison; Antonia L Pritchard Journal: Pigment Cell Melanoma Res Date: 2022-03-04 Impact factor: 4.159