Significant differences in outcome between Immunoscore ... · in 2 categories (IS0-1 vs IS 2-3-4)...
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Jérôme Galon 1 , Fabienne Hermitte 2 , Bernhard Mlecnik 1,3 , Florence Marliot 1,4 , Carlo Bifulco 5 , Alessandro Lugli 6 , Iris D Nagtegaal 7 , Arndt Hartmann 8 , Marc Van den Eynde 9 , Michael H A Roehrl 10 , Pamela S Ohashi 11 , Eva Zavadova 12 , Toshihiko Torigoe 13 , Prabhu S Patel 14 , Yili Wang 15 , Yutaka Kawakami 16 , Francesco M Marincola 17 , Paolo A Ascierto 18 , Bernard A Fox 19 , Franck Pagès 1,4 1 INSERM, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot; Centre de Recherche des Cordeliers, Paris, FR; 2 HalioDx, Marseille, FR; 3 Inovarion, Paris, FR; 4 Laboratory of Immunology, AP-HP, Georges Pompidou European Hospital, Paris, FR; 5 Department of Pathology, Providence Portland Medical Center, Portland, OR, US; 6 Institute of Pathology, University of Bern, Bern, CH; 7 Pathology, Radboud University Medical Centre Nijmegen, Nijmegen, NL; 8 Department of Surgery,University Erlangen-Nürnberg, Erlangen, DE; 9 Department of Medical Oncology, Cliniques Universitaires St. Luc, Brussels, BE; 10 Department of Pathology, Memorial Sloan Kettering Cancer Center, New-York, NY, US; 11 Princess Margaret Cancer Centre, University Health Network, Toronto, ON, CA; 12 Pathology, General Faculty Hospital, VFN Charles University, Prague, CZ; 13 Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, JP; 14 Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, IN; 15 Institute for Cancer Research, School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, Xian,CN; 16 Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, JP; 17 Refuge Biotechnologies, Menlo Park, CA, US; 18 Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Instituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Napoli, IT; 19 Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Portland, US. Significant differences in outcome between Immunoscore categories in stage I colon cancer patients • A subgroup analysis was performed on the stage I patients (n=451) from the Immunoscore international validation study (Pagès et al. The Lancet 2018). Patients were classified by Immunoscore based on pre- defined cutoffs, either in 5 (IS 0-4), in 3 (IS 0-1, IS 2, IS 3-4) or in 2 categories (IS 0-1,IS 2-3-4) • Time to recurrence (TTR) was compared between Immunoscore categories. Immunoscore® is an in vitro diagnostic test that predicts the risk of relapse in patients with early-stage Colon Cancer (CC) by measuring the host immune response at the tumor site. It is a risk-assessment tool that provides independent and superior prognostic value than traditional risk parameters and is intended to be used as an adjunct to the TNM classification. Currently, the target population for Immunoscore is stage II & III CC patients, for whom individual risk-assessment plays a critical role to guide post-surgery decisions. In stage I, survival rates are high and adjuvant chemotherapy is not typically recommended. However, approximately 10% of stage I CC tumors will recur even after surgical resection. Distribution of Immunoscore among 451 Stage I CC patients Association of Immunoscore with clinical outcome in Stage I Colon Cancer Patients • Pagès F, Mlecnik B, Marliot F et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 2018 • Mlecnik B, Bindea G, Angell HK et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity 2016 • Sinicrope F, Shi Q, Hermitte F et al. Immunoscore to provide prognostic information in low- (T1-3N1) and high-risk (T4 or N2) subsets of Stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance). J Clin Oncol 2018; 36:4s (suppl; abstr 614) • Pages F, Andre T, Taieb J et al. Validation of the Immunoscore prognostic value in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France cohort study (PRODIGE-GERCOR). J Clin Oncol 2019 37:15s (suppl; abst 3513) • Pagès F, Mlecnik B, Marliot F et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 2018 • Mlecnik B, Bindea G, Angell HK et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity 2016 • Sinicrope F, Shi Q, Hermitte F et al. Immunoscore to provide prognostic information in low- (T1-3N1) and high-risk (T4 or N2) subsets of Stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance). J Clin Oncol 2018; 36:4s (suppl; abstr 614) • Pages F, Andre T, Taieb J et al. Validation of the Immunoscore prognostic value in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France cohort study (PRODIGE-GERCOR). J Clin Oncol 2019 37:15s (suppl; abst 3513) Fig. 1. Stratification of TTR by IS in 2 categories (IS0-1 vs IS 2-3-4) Fig. 2 Stratification of TTR by IS in 3 categories (IS0-1 vs IS 2 vs IS 3-4) Fig.3 Stratification of TTR by IS in 5 categories (IS 0 to IS 4) Relative contribution of IS to the risk of relapse (Chi2) • Immunoscore was stronger than all standard clinical parameters, showing the highest contribution to predict relapse • Similar significant results were found using the Immunoscore percentiles as numeric continuous parameter • IS 3-4, 2 and 0-1 were observed in 39%, 47% and 14% of the cohort, respectively. • IS was positively and significantly correlated with TTR. • In multivariate analysis, when adjusting the model with IS, age, gender, T-stage sidedness and MSI, IS remained the sole significant parameter (stratified by participating center HR low vs high =7.82; 95% CI 1.49−41.01; p=0.015), with the highest relative contribution for prediction of relapse (chi squared proportion (χ²) =62%) compared to the other parameters in the model. • Immunoscore is a robust prognostic indicator of the risk of recurrence in stage I CC. • This risk assessment tool reliably identifies a sub-group of patients with an increased risk of relapse for whom a more intensive surveillance program after curative resection may be recommended. Immunoscore classification Events/total 5y event-free survival IS4 1/27 100% IS3 4/149 96.6% IS2 13/214 94.9% IS1 4/45 90.5% IS0 2/16 92.3% Correlation between Immunoscore classification and TTR IS 0-1 IS 2-3-4 IS 0-1 IS 2 IS 2-3-4
Transcript of Significant differences in outcome between Immunoscore ... · in 2 categories (IS0-1 vs IS 2-3-4)...
Jérôme Galon1, Fabienne Hermitte2, Bernhard Mlecnik1,3, Florence Marliot1,4, Carlo Bifulco5, Alessandro Lugli6, Iris D Nagtegaal7, Arndt Hartmann8,Marc Van den Eynde9, Michael H A Roehrl10, Pamela S Ohashi11, Eva Zavadova12, Toshihiko Torigoe13, Prabhu S Patel14, Yili Wang15, Yutaka Kawakami16,Francesco M Marincola17, Paolo A Ascierto18, Bernard A Fox19, Franck Pagès1,4
1INSERM, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot; Centre de Recherche desCordeliers, Paris, FR; 2HalioDx, Marseille, FR; 3Inovarion, Paris, FR; 4Laboratory of Immunology, AP-HP, Georges Pompidou European Hospital, Paris, FR; 5Department of Pathology, Providence Portland Medical Center, Portland,OR, US; 6Institute of Pathology, University of Bern, Bern, CH; 7Pathology, Radboud University Medical Centre Nijmegen, Nijmegen, NL; 8Department of Surgery,University Erlangen-Nürnberg, Erlangen, DE; 9Department of MedicalOncology, Cliniques Universitaires St. Luc, Brussels, BE; 10Department of Pathology, Memorial Sloan Kettering Cancer Center, New-York, NY, US; 11Princess Margaret Cancer Centre, University Health Network, Toronto, ON, CA;12Pathology, General Faculty Hospital, VFN Charles University, Prague, CZ; 13Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, JP; 14Cancer Biology, The Gujarat Cancer & Research Institute,Ahmedabad, IN; 15Institute for Cancer Research, School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, Xian,CN; 16Division of CellularSignaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, JP; 17Refuge Biotechnologies, Menlo Park, CA, US; 18Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, InstitutoNazionale Tumori – I.R.C.C.S - Fondazione Pascale, Napoli, IT; 19Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Portland, US.
Significant differences in outcome between Immunoscore categories in stage I colon cancer patients
• A subgroup analysis was performed on the stage I patients (n=451)from the Immunoscore international validation study (Pagès et al. TheLancet 2018). Patients were classified by Immunoscore based on pre-defined cutoffs, either in 5 (IS 0-4), in 3 (IS 0-1, IS 2, IS 3-4) or in 2categories (IS 0-1,IS 2-3-4)
• Time to recurrence (TTR) was compared between Immunoscorecategories.
Immunoscore® is an in vitro diagnostic test that predicts the risk ofrelapse in patients with early-stage Colon Cancer (CC) by measuring thehost immune response at the tumor site. It is a risk-assessment tool thatprovides independent and superior prognostic value than traditional riskparameters and is intended to be used as an adjunct to the TNMclassification. Currently, the target population for Immunoscore is stage II& III CC patients, for whom individual risk-assessment plays a critical roleto guide post-surgery decisions. In stage I, survival rates are high andadjuvant chemotherapy is not typically recommended. However,approximately 10% of stage I CC tumors will recur even after surgicalresection.
Distribution of Immunoscore among 451 Stage I CC patients
Association of Immunoscore with clinical outcome inStage I Colon Cancer Patients
• Pagès F, Mlecnik B, Marliot F et al. International validation of the consensus Immunoscore for the classification of colon cancer: aprognostic and accuracy study. Lancet 2018
• Mlecnik B, Bindea G, Angell HK et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor ofPatient Survival Than Microsatellite Instability. Immunity 2016
• Sinicrope F, Shi Q, Hermitte F et al. Immunoscore to provide prognostic information in low- (T1-3N1) and high-risk (T4 or N2)subsets of Stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance). J ClinOncol 2018; 36:4s (suppl; abstr 614)
• Pages F, Andre T, Taieb J et al. Validation of the Immunoscore prognostic value in stage III colon cancer patients treated withoxaliplatin in the prospective IDEA France cohort study (PRODIGE-GERCOR). J Clin Oncol 2019 37:15s (suppl; abst 3513)
• Pagès F, Mlecnik B, Marliot F et al. International validation of the consensus Immunoscore for the classification of colon cancer: aprognostic and accuracy study. Lancet 2018
• Mlecnik B, Bindea G, Angell HK et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor ofPatient Survival Than Microsatellite Instability. Immunity 2016
• Sinicrope F, Shi Q, Hermitte F et al. Immunoscore to provide prognostic information in low- (T1-3N1) and high-risk (T4 or N2)subsets of Stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance). J ClinOncol 2018; 36:4s (suppl; abstr 614)
• Pages F, Andre T, Taieb J et al. Validation of the Immunoscore prognostic value in stage III colon cancer patients treated withoxaliplatin in the prospective IDEA France cohort study (PRODIGE-GERCOR). J Clin Oncol 2019 37:15s (suppl; abst 3513)
Fig. 1. Stratification of TTR by IS in 2 categories (IS0-1 vs IS 2-3-4)
Fig. 2 Stratification of TTR by ISin 3 categories (IS0-1 vs IS 2 vs IS 3-4)
Fig.3 Stratification of TTR by ISin 5 categories (IS 0 to IS 4)
Relative contribution of IS to the risk of relapse (Chi2)
• Immunoscore was strongerthan all standard clinicalparameters, showing thehighest contribution topredict relapse
• Similar significant resultswere found using theImmunoscore percentilesas numeric continuousparameter
• IS 3-4, 2 and 0-1 were observed in 39%, 47% and 14% of the cohort,respectively.
• IS was positively and significantly correlated with TTR.• In multivariate analysis, when adjusting the model with IS, age, gender,
T-stage sidedness and MSI, IS remained the sole significant parameter(stratified by participating center HRlow vs high=7.82; 95% CI 1.49−41.01;p=0.015), with the highest relative contribution for prediction ofrelapse (chi squared proportion (χ²) =62%) compared to the otherparameters in the model.
• Immunoscore is a robust prognostic indicator of the risk ofrecurrence in stage I CC.
• This risk assessment tool reliably identifies a sub-group of patientswith an increased risk of relapse for whom a more intensivesurveillance program after curative resection may berecommended.
Immunoscore classification
Events/total5y event-free
survivalIS4 1/27 100%IS3 4/149 96.6%IS2 13/214 94.9%IS1 4/45 90.5%IS0 2/16 92.3%
Correlation between Immunoscore classification and TTR
IS 0-1IS 2-3-4
IS 0-1IS 2IS 2-3-4
