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

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

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.

Highlights

Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study
Mutated immunoglobulin heavy chain variable (IGHV) status was significantly associated with lower levels of soluble CD23 (sCD23) and higher levels of nuclear factor of activated T cells 3 (NFATC3), while a positive association between b2M levels and 58 markers was established (Supplementary Table E3, online only, available at www.exphem.org)
Because of the limited sample size of our study resulting in the wide confidence intervals, these findings should be interpreted with caution and require validation in larger studies. In this pilot study, we were able to validate sCD23 levels above the median as significantly associated with a shorter event-free survival (EFS), which is consistent with previous studies [7]

Summary

Introduction

Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study. 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. FSH and AWL contributed to the data analysis. AWL and MDL contributed to the data analysis and writing of the article. The identification of new prognostic parameters that are able to predict clinical outcome after treatment is important for patient management and may be useful in guiding therapeutic decisions

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Conclusion