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

• Published in: Experimental hematology Vol. 89; pp. 55 - 60.e6
• Main Authors: Saberi Hosnijeh, Fatemeh, van der Straten, Lina, Kater, Arnon P., van Oers, Marinus H.J., Posthuma, Ward F.M., Chamuleau, Martine E.D., Bellido, Mar, Doorduijn, Jeanette K., van Gelder, Michel, Hoogendoorn, Mels, de Boer, Fransien, te Raa, G. Doreen, Kerst, J. Martijn, Marijt, Erik W.A., Raymakers, Reinier A.P., Koene, Harry R., Schaafsma, Martijn R., Dobber, Johan A., Tonino, Sanne H., Kersting, Sabina S., Langerak, Anton W., Levin, Mark-David
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.2020
• Subjects: 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
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2020.08.002

•The prognostic ability of IGHV mutational status and sex was validated in this cohort.•The markers sCD23, SPINT1, and LY9 have possible prognostic ability for EFS in CLL patients.•Patients with these marker levels above the median had a shorter EFS than those with marker levels below the median.•Unmutated IGHV patients with an sCD23 or sCD27 level above the median had the lowest EFS. 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.