ABSTRACT
The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.
Subject(s)
B7-H1 Antigen , Lymphoma , Humans , B7-H1 Antigen/metabolism , Prognosis , Central Nervous System , Lymphoma/diagnosisABSTRACT
BACKGROUND: The therapeutic options of relapsed or refractory multiple myeloma (RRMM) remain a challenge. The MM-003 trial demonstrated that RRMM patients treated with pomalidomide and dexamethasone (Pom/Dex) have better progression-free survival (PFS) than those treated with high-dose dexamethasone alone. However, the real-world effectiveness of Pom/Dex in these patients in Taiwan remains unclear. METHODS: This multicenter, registry-based study retrospectively reviewed the medical records of 49 consecutive patients undergoing Pom/Dex treatment for RRMM. We investigated the overall response rate (ORR) and PFS in these patients. The patients were stratified into two groups: those who received two (n=33) and those who received more than two (n=16) prior lines of treatment according to the numbers of regimens before Pom/Dex therapy. The differences in ORR and PFS between these two groups were further analyzed. We also analyzed factors attributed to disease progression. RESULTS: The ORR was 47.7%, and the median PFS was 4.0 months (range, 0.1-21.1). Patients who received two prior lines of treatment had a higher ORR than those who received more than two prior lines of treatment (55.2% vs. 33.3%; p=0.045). The median PFS of these groups was 4.8 and 3.9 months, respectively (p=0.805). Primary lenalidomide refractoriness reduced the risk of myeloma progression following Pom/Dex treatment (hazard ratio, 0.14; p=0.001). CONCLUSIONS: The median PFS following Pom/Dex treatment in Taiwanese RRMM patients in a real-world setting was similar to that reported by the MM-003 trial. Primary lenalidomide refractoriness should not be an obstacle for Pom/Dex treatment in RRMM.
ABSTRACT
The surface of superparamagnetic iron oxide nanoparticles (SPIO) with different molecular weight of poly(ethylene glycol) (PEG) and folic acid (FA) were synthesized. The SPIO-PEG-FA nanoparticles are well-dispersed and have good stability in various pH solutions. The lack of hysterestis and remanence at ambient temperatures is characteristic of superparamagnetic materials for SPIO-PEG-FA. The uptake by macrophage for SPIO-PEG-FA is lower than that of Feridex I.V. even at higher concentration. Internalization of SPIO-PEG-FA in targeted cells (KB cells) was observed by flow-cytometric analysis and in vitro MR imaging. The intensity change of positive KB cell tumor (-20 to 25%) is significantly lower than that of negative HT-1080 cell tumor from precontrast to postcontrast images of the tumor by in vivo MR imaging. These preliminary results demonstrated that SPIO-PEG-FA have the ability to target folate receptor.
