Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Laponite intercalated biomimetic multilayer coating prevents glucocorticoids induced orthopedic implant failure

Implant failure,which is commonly associated with failure of osseointegration and peri-implant infection,is a severe complication of orthopedic surgery.In particular,the survival rate of implants is significantly decreased in patients using long-term glucocorticoids(GCs).However,the exact molecular mechanism underlying GCs-induced implant loosening,as well as preventive strategies for these patients,is unclear.To address this problem,we performed RNA-sequencing and found that WNT16 was correlated with GCs-induced osteopenia(LogFC=-5.17,p<0.01).Inspired by the concept of“organic-inorganic”hybrid,we theorized to introduce a bioactive two-dimensional nanosheet into a layer-by-layer(LbL)self-assembly coating to construct a customized implant that targets WNT16.After screening commercially available nanosheets,laponite(LAP)was identified as a cost-effective rescuer for GCs-induced WNT16 inhibition,which was then intercalated into LbL deposition system consisting of quaternized chitosan(QCS)and hyaluronic acid(HA).The hybrid coating(QCS/HA/LAP)showed micrometer thickness and improved hydrophilicity and interface roughness.Furthermore,QCS/HA/LAP coated polyetheretherketone(PEEK)implant enhanced cell viability,adhesion,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs),and promoted osteointegration of PEEK in GCs-treated rats by targeting the WNT16/β-catenin axis.The assembled QCS has proven antibacterial properties,and the hybrid coating exerted potent detrimental effects against methicillin-resistant Staphylococcus aureus(MRSA)and Escherichia coli(E.coli),both in vitro and in vivo.Taken together,these results suggest that QCS/HA/LAP coating has great potential for use in implants customization,and has synergistic pro-osteogenic and antibacterial effects that help prevent implant failure in GCs-treated patients.