C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer
Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as a pre...
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BMJ Publishing Group
2022-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/3/e004024.full |
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| author | Stefan Diem Markus Joerger Fiamma Berner Lukas Flatz Niklas Klümper Manuel Ritter Michael Hölzel Jörg Ellinger Peter Brossart Annkristin Heine Jonas Saal Christa Lichtensteiger Nina Wyss Franz Georg Bauernfeind Sabine Schmid Martin Frueh Tobias Bald |
| author_facet | Stefan Diem Markus Joerger Fiamma Berner Lukas Flatz Niklas Klümper Manuel Ritter Michael Hölzel Jörg Ellinger Peter Brossart Annkristin Heine Jonas Saal Christa Lichtensteiger Nina Wyss Franz Georg Bauernfeind Sabine Schmid Martin Frueh Tobias Bald |
| author_sort | Stefan Diem |
| collection | DOAJ |
| description | Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as a predictive on-treatment biomarker. In a retrospective (N=105) and prospective (N=108) ICB-treated NSCLC cohort, early CRP kinetics were stratified after the start of immunotherapy until weeks 4, 6, and 12 as follows: an early doubling of baseline CRP followed by a drop below baseline (CRP flare-responder), a drop of at least 30% below baseline without prior flare (CRP responders), or those who remained as CRP non-responders. In our study, we observed characteristic longitudinal changes of serum CRP concentration after the initiation of ICB. In the prospective cohort, N=40 patients were defined as CRP non-responders, N=39 as CRP responders, and N=29 as CRP flare-responders with a median progression-free survival (PFS) of 2.4, 8.1, and 14.3 months, respectively, and overall survival (OS) of 6.6, 18.6, and 32.9 months (both log-rank p<0.001). Of note, CRP flare-responses, characterized by a sharp on-treatment CRP increase in the first weeks after therapy initiation, followed by a decrease of CRP serum level below baseline, predict ICB response as early as 4 weeks after therapy initiation. Of note, early CRP kinetics showed no predictive value for chemoimmunotherapy or when steroids were administered concurrently. On-treatment CRP kinetics had a predictive value for both major histological NSCLC subtypes, adenocarcinoma and squamous cell carcinoma. The results were verified in an independent retrospective cohort of 105 patients. In conclusion, CRP flare predicted anti-PD-1 monotherapy response and survival in two independent cohorts including a total of 213 patients with NSCLC, regardless of histology. Due to its wide clinical availability, early CRP kinetics could become an easily determined, cost-efficient, and non-invasive biomarker to predict response to checkpoint inhibitors in NSCLC within the first month. |
| format | Article |
| id | doaj-art-a419b057817a4ab6b93221e6e2d22e8a |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a419b057817a4ab6b93221e6e2d22e8a2025-08-20T03:05:22ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-03-0110310.1136/jitc-2021-004024C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancerStefan Diem0Markus Joerger1Fiamma Berner2Lukas Flatz3Niklas Klümper4Manuel Ritter5Michael Hölzel6Jörg Ellinger7Peter Brossart8Annkristin Heine9Jonas Saal10Christa Lichtensteiger11Nina Wyss12Franz Georg Bauernfeind13Sabine Schmid14Martin Frueh15Tobias Bald16Department of Oncology and Hematology, Kantonsspital St Gallen, St Gallen, SwitzerlandDepartment of Oncology and Hematology, Kantonsspital St Gallen, St. Gallen, SwitzerlandInstitute of Immunobiology, Kantonsspital St Gallen, St Gallen, SwitzerlandInstitute of Immunobiology, Kantonsspital St Gallen, St Gallen, SwitzerlandInstitute for Experimental Oncology, University Hospital Bonn, Bonn, Germany1 Department of Urology, University Hospital Bonn, Bonn, GermanyInstitute of Experimental Oncology, University Medical Center Bonn (UKB), Bonn, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Bonn (UKB), Bonn, GermanyDepartment of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany2Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Bonn, GermanyMedical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Hospital Bonn, Bonn, GermanyInstitute of Immunobiology, Kantonsspital St Gallen, St Gallen, SwitzerlandInstitute of Immunobiology, Kantonsspital St Gallen, St Gallen, SwitzerlandDepartment of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, GermanyDepartment of Oncology and Hematology, Kantonsspital St Gallen, St Gallen, SwitzerlandDepartment of Oncology and Hematology, Kantonsspital St Gallen, St Gallen, SwitzerlandInstitute for Experimental Oncology, University Hospital Bonn, Bonn, GermanyBiomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as a predictive on-treatment biomarker. In a retrospective (N=105) and prospective (N=108) ICB-treated NSCLC cohort, early CRP kinetics were stratified after the start of immunotherapy until weeks 4, 6, and 12 as follows: an early doubling of baseline CRP followed by a drop below baseline (CRP flare-responder), a drop of at least 30% below baseline without prior flare (CRP responders), or those who remained as CRP non-responders. In our study, we observed characteristic longitudinal changes of serum CRP concentration after the initiation of ICB. In the prospective cohort, N=40 patients were defined as CRP non-responders, N=39 as CRP responders, and N=29 as CRP flare-responders with a median progression-free survival (PFS) of 2.4, 8.1, and 14.3 months, respectively, and overall survival (OS) of 6.6, 18.6, and 32.9 months (both log-rank p<0.001). Of note, CRP flare-responses, characterized by a sharp on-treatment CRP increase in the first weeks after therapy initiation, followed by a decrease of CRP serum level below baseline, predict ICB response as early as 4 weeks after therapy initiation. Of note, early CRP kinetics showed no predictive value for chemoimmunotherapy or when steroids were administered concurrently. On-treatment CRP kinetics had a predictive value for both major histological NSCLC subtypes, adenocarcinoma and squamous cell carcinoma. The results were verified in an independent retrospective cohort of 105 patients. In conclusion, CRP flare predicted anti-PD-1 monotherapy response and survival in two independent cohorts including a total of 213 patients with NSCLC, regardless of histology. Due to its wide clinical availability, early CRP kinetics could become an easily determined, cost-efficient, and non-invasive biomarker to predict response to checkpoint inhibitors in NSCLC within the first month.https://jitc.bmj.com/content/10/3/e004024.full |
| spellingShingle | Stefan Diem Markus Joerger Fiamma Berner Lukas Flatz Niklas Klümper Manuel Ritter Michael Hölzel Jörg Ellinger Peter Brossart Annkristin Heine Jonas Saal Christa Lichtensteiger Nina Wyss Franz Georg Bauernfeind Sabine Schmid Martin Frueh Tobias Bald C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer Journal for ImmunoTherapy of Cancer |
| title | C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer |
| title_full | C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer |
| title_fullStr | C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer |
| title_full_unstemmed | C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer |
| title_short | C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer |
| title_sort | c reactive protein flare predicts response to checkpoint inhibitor treatment in non small cell lung cancer |
| url | https://jitc.bmj.com/content/10/3/e004024.full |
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