Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study

Fatemeh Saberi Hosnijeh; Lina van der Straten; Arnon P Kater; Marinus H J van Oers; Ward F M Posthuma; Martine E D Chamuleau; Mar Bellido; Jeanette K Doorduijn; Michel van Gelder; Mels Hoogendoorn; Fransien de Boer; G Doreen Te Raa; J Martijn Kerst; Erik W A Marijt; Reinier A P Raymakers; Harry R Koene; Martijn R Schaafsma; Johan A Dobber; Sanne H Tonino; Sabina S Kersting; Anton W Langerak; Mark-David Levin

doi:10.1016/j.exphem.2020.08.002

Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study

Exp Hematol. 2020 Sep:89:55-60.e6. doi: 10.1016/j.exphem.2020.08.002. Epub 2020 Aug 8.

Authors

Fatemeh Saberi Hosnijeh¹, Lina van der Straten², Arnon P Kater³, Marinus H J van Oers³, Ward F M Posthuma⁴, Martine E D Chamuleau⁵, Mar Bellido⁶, Jeanette K Doorduijn⁷, Michel van Gelder⁸, Mels Hoogendoorn⁹, Fransien de Boer¹⁰, G Doreen Te Raa¹¹, J Martijn Kerst¹², Erik W A Marijt¹³, Reinier A P Raymakers¹⁴, Harry R Koene¹⁵, Martijn R Schaafsma¹⁶, Johan A Dobber¹⁷, Sanne H Tonino¹⁸, Sabina S Kersting¹⁹, Anton W Langerak²⁰, Mark-David Levin²¹

Affiliations

¹ Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands. Electronic address: [email protected].
² Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
³ Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
⁴ Department of Internal Medicine, Reinier de Graaf Hospital, Delft, The Netherlands; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
⁶ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
⁸ Department of Hematology, University Medical Center, Maastricht, The Netherlands.
⁹ Department of Internal Medicine, Medical Center, Leeuwarden, The Netherlands.
¹⁰ Department of Internal Medicine, Ikazia Hospital, Rotterdam, The Netherlands.
¹¹ Department of Internal Medicine, Gelderland Valley Hospital, Ede, The Netherlands.
¹² Department of Medical Oncology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹³ Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁴ Department of Hematology, University Medical Center, Utrecht, The Netherlands.
¹⁵ Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands.
¹⁶ Department of Hematology, Medical Spectrum Twente, Enschede, The Netherlands.
¹⁷ Laboratory Special Hematology, Academic Medical Center, Amsterdam, The Netherlands.
¹⁸ Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
¹⁹ Department of Hematology, Haga Hospital, The Hague, The Netherlands.
²⁰ Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
²¹ Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.

PMID: 32781097
DOI: 10.1016/j.exphem.2020.08.002

Abstract

Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25-60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients.

Publication types

Clinical Trial, Phase I
Clinical Trial, Phase II

MeSH terms

Aged
Aged, 80 and over
Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / blood
Biomarkers, Tumor / genetics*
Chlorambucil
Disease-Free Survival
Female
Gene Expression
Humans
Immunoglobulin Heavy Chains / blood
Immunoglobulin Heavy Chains / genetics
Immunotherapy / methods
Lenalidomide
Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
Leukemia, Lymphocytic, Chronic, B-Cell / genetics
Leukemia, Lymphocytic, Chronic, B-Cell / mortality
Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
Male
Middle Aged
Mutation
Prognosis
Proteinase Inhibitory Proteins, Secretory / blood
Proteinase Inhibitory Proteins, Secretory / genetics*
Proteomics / methods
Receptors, IgE / blood
Receptors, IgE / genetics*
Rituximab
Signaling Lymphocytic Activation Molecule Family / blood
Signaling Lymphocytic Activation Molecule Family / genetics*
Treatment Outcome
Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood
Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics

Substances

Antineoplastic Agents
Biomarkers, Tumor
Immunoglobulin Heavy Chains
LY9 protein, human
Proteinase Inhibitory Proteins, Secretory
Receptors, IgE
SPINT1 protein, human
Signaling Lymphocytic Activation Molecule Family
Tumor Necrosis Factor Receptor Superfamily, Member 7
Chlorambucil
Rituximab
Lenalidomide