Levels of soluble CD163 appear to be higher in those with p53 abnormalities, elevated lactate dehydrogenase, and low hemoglobin in a study cohort of patients with mantle cell lymphoma.
High levels of the soluble M2 macrophage marker CD163 correlated with worse survival outcomes regardless of receipt of chemoimmunotherapy or targeted therapy in patients with mantle cell lymphoma (MCL), according to findings from a study published in Blood Advances.
According to univariate analyses, the presence of high CD163 levels correlated with shorter progression-free survival (PFS; P = .002) and overall survival (OS; P <.001). The 5-year OS rate in patients with low and high CD163, respectively, were 97% (95% CI, 93%-100%) vs 51% (95% CI, 34%-75%). In patients with relapsed MCL, high CD163 also correlated with worse PFS (P = .016) and OS (P = .035).
After adjusting for age and sex, and stratifying patients by time of sampling, investigators still identified a relationship between high CD163 and shorter PFS (HR, 3.13; 95% CI, 1.83-5.36) and OS (HR, 4.10; 95% CI, 2.06-8.16). Moreover, high CD163 also correlated with worse PFS (HR, 3.48; 95% CI, 1.42-8.54) and OS (HR, 4.33; 95% CI, 1.32-14.2) in a fully adjusted regression model accounting for MCL International Prognostic Index (MIPI), Ki67, histology, and p53 status.
“The results from this study further enhance the important role of M2-like macrophages in MCL. The emerging treatments directed towards these macrophages are of interest for patients [with MCL] with high [soluble] CD163,” the study authors wrote.
“We propose that [soluble] CD163 could be used as a prognostic marker in both newly diagnosed and relapsed MCL, perhaps supporting clinicians in de-escalating treatment in elderly or fragile patients with low [soluble] CD163. It could also be an easily accessible biomarker used together with TP53 or blastoid/pleomorphic histology when selecting patients for more intense treatment.”
Investigators of this study assessed data from 2 population-based cohorts, which included samples taken from patients with MCL in Lund (n = 49) and Uppsala (n = 32), Sweden. The study also included a cohort of patients with relapsed MCL (n = 44) who were enrolled on the phase 2 PHILEMON trial (NCT02460276), in which investigators evaluated rituximab (Rituxan) plus ibrutinib (Imbruvica) and lenalidomide (Revlimid) as a treatment for MCL.
Investigators assessed soluble CD163 levels in pre-treatment serum samples using an ELISA immunoassay. A p53 abnormality was defined as a TP53 mutation or p53 overexpression identified through immunohistochemistry, and a low hemoglobin (Hb) level was defined as below the reference value of 120 g/L for female patients and 130 g/L for male patients.
Samples were collected from 81 patients at diagnosis and from 50 patients who had relapsed. Moreover, 53% of patients were under 70 years old, and 73% were male. Across all patients, most had an ECOG performance status of 0 to 1 (97%), a MIPI score of 3 (43%), normal lactate dehydrogenase (LDH) levels (55%), normal Hb levels (56%), and classic histology (76%). The median follow-up time in the population-based cohort was 4.3 years (range, 0.11-9.8), and 43% of patients experienced a relapse or died during follow-up.
Patients with relapsed disease received a median of 2 (range, 1-5) prior lines of treatment in the PHILEMON trial cohort. The median follow-up in this cohort was 3.5 years (range, 0.1-4.2), and 59% of patients had died or experienced a relapse during follow-up.
The median CD163 level was 3211 ng/mL (range, 1311-7611) in samples taken at diagnosis and 2963 ng/mL (range, 1223-6002) in samples taken at relapse. The overall median CD163 level was 3112 ng/mL (range, 1223-7611).
Investigators observed higher levels of CD163 in patients with p53 abnormalities. The same was true for patients with elevated LDH and those with low Hb.
Investigators analyzed CD163 levels in MCL lymphoma tissue across 29 patients, and reported that the marker appeared to predict poor PFS based on a multivariate Cox regression model (HR, 4.0; 95% CI, 1.05-15.16). A higher rate of CD163 occurred across 3 samples with p53 overexpression compared with tumors that had no p53 expression.
Soluble CD163 levels that investigators measured during remission after patients completed treatment identified those who did not experience disease progression within 24 months. Additionally, no patient with low CD163 levels during remission experienced a relapse within 24 months.
Nikkarinen A, Lokhande L, Amini R, et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. Published online June 30, 2023. doi:10.1182/bloodadvances.2023010052