Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma.

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). We aimed to investigate the prognostic value of sCD163 in 131 MCL patients. We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) (p=0.002 and p<0.001) in 81 newly diagnosed chemoimmunotherapy-treated patients. The same was seen in a cohort of 50 relapsed MCL patients mainly treated within the phase II Philemon-trial with rituximab, ibrutinib and lenalidomide (PFS p=0.016 and OS p=0.035). In newly diagnosed patients with low levels of sCD163, five-year survival was 97%. There was a moderate correlation between sCD163 and tissue CD163 (r=0.64, p=0.014). The association 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), showing that high levels of the M2 macrophage marker sCD163 is an independent negative prognostic factor in MCL, both in the chemoimmunotherapy and ibrutinib/lenalidomide era. In addition, low sCD163 levels identify MCL patients with a very good prognosis.