Soluble macrophage marker scd163 predicts outcome in both chemoimmunotherapy and targeted therapy treated mantle cell lymphoma

Introduction: The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed towards the tumor immune microenvironment, where macrophages play an important role. In MCL, the presence of M2 macrophages defined by CD163 expression in diagnostic biopsies has been associated with a worse prognosis. An alternative way to assess the abundance of M2 macrophages is by measuring the level of soluble CD163 in serum (sCD163). Method: We aimed to investigate the prognostic value of sCD163 in 131 MCL patients. sCD163 was analyzed with ELISA and the cut-off was á priori set to median level. Results: We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) (log rank test p = 0.002 and p < 0.001, respectively) in 81 newly diagnosed patients that were subsequently treated with chemoimmunotherapy. The same was seen in a cohort of 50 relapsed, heavily pretreated, MCL patients mainly treated within the phase II Philemon-trial with rituximab, ibrutinib and lenalidomide (log rank test, PFS p = 0.016 and OS p = 0.035). Low levels of sCD163 at diagnosis identified patients with a very good prognosis, as shown by a five-year OS of 97%. There was a moderate correlation between sCD163 and tissue CD163 from MCL lymph nodes (r = 0.64, p = 0.014). sCD163 was higher in TP53-mutated/p53 high cases. However, the association of high sCD163 with a poor prognosis was independent of MIPI, Ki67, p53 status and blastoid morphology, as assessed in a multivariable cox proportional hazards model. Here, high sCD163 was associated with both shorter PFS (HR 3.48 95% CI: 1.42–8.54) and shorter OS (HR 4.33 95% CI: 1.32–14.2). The research was funded by: The study was supported by grants from the Swedish Cancer Society (19 0123 Pj 01 H and 19 0109 SCIA, to I.G), the Swedish Society of Medicine (I.G), Lions Cancer Research Fund (I.G), Financial support for SE was granted by the European Union’s Horizon 2020 Framework Programme for Research and Innovation under agreement 754299, Cancerfonden (21 1561 Pj), Mats Paulsson’s Foundation for research, innovation och societal development, Stefan Paulsson’s Cancer Foundation, and CREATE Health. Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, microenvironment Conflicts of interests pertinent to the abstract M. Jerkeman Honoraria: AstraZeneca, Genmab, Kite/Gilead, Incyte, Orion, Novartis, Roche, Janssen, BMS, Abbvie (not related to this study) Research funding: AstraZeneca, Kite/Gilead, Roche, Janssen, BMS, Abbvie D. Molin Research funding: Roche, Merck, Bristol-Myers Squibb, and Takeda (not related to this study) G. Enblad Consultant or advisory role Advisory Board of Gilead and Pierre Fabre, scientific advisor for Elicera Therapeutics AB, Sprint Bioscience AB and XNK Therapeutics AB Honoraria: Gilead, Pierre Fabre and Roche C. E. Weibull Employment or leadership position: War On Cancer Consultant or advisory role Red Door Analytics Research funding: Janseen Cilag S. Ek Research funding: European Union’s Horizon 2020 Framework Programme for Research and Innovation under agreement 754299, Cancerfonden (21 1561 Pj), Mats Paulsson’s Foundation for research, innovation och societal development, Stefan Paulsson’s Cancer Foundation, and CREATE Health. I. Glimelius Honoraria: Janssen-Cilag and Takeda (not related to this study).