methotrexate IV

To evaluate the intracranial delivery of BTK inhibitor(BTKi), patient-derived PCNS-LBCL xenografted mice models were treated with highly-selective BTKi orelabrutinib, either monotherapeutically or in combining with methotrexate...The mutations in CSF circulating tumor DNA (ctDNA) rather than plasma-ctDNA were more consistent to those in tumor tissue, indicating that CSF-ctDNA is a useful tool for monitoring PCNS-LBCL. In summary, our data provided the molecular rationale as well as clinical evidences that incorporation of BTKi into frontline induction therapy is a promising strategy for ND PCNS-LBCL.

The patient was treated with Pola-R-CHP followed by CNS-directed therapy, including high-dose methotrexate and intrathecal chemotherapy...Tumor-associated RANKL expression may be associated with the osteolytic features observed in this case. Early biopsy and systemic evaluation of cutaneous lesions are essential, as they may reflect aggressive systemic disease.

The current standard of care for induction treatment is based on high-dose methotrexate as the central component, followed by consolidating high-dose chemotherapy and autologous stem cell transplantation in eligible patients...Given the significant prognostic and therapeutic implications of the immune microenvironment, its impact should be reflected and validated in future standard risk stratifications. Integrating validated immune biomarkers with emerging immunotherapeutic strategies has the potential not only to improve individual patient outcomes but also to optimize the overall structure of care for patients with PCNSL.

P2/3, N=131, Recruiting, National Cancer Institute (NCI) | N=249 --> 131

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: May 2026 --> Sep 2026

P2, N=293, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Apr 2026 --> Apr 2029

For fit patients, the current gold standard remains intensive induction with high-dose methotrexate (HD-MTX)-based polychemotherapy followed by thiotepa-conditioned autologous stem cell transplantation (ASCT)...Furthermore, evidence from international registries has shown promising activity of chimeric antigen receptor T (CAR-T) in relapsed/refractory patients, with acceptable toxicity. Looking ahead, the translation of circulating tumor DNA profiling "from bench to bedside" for measurable residual disease monitoring, alongside the integration of AI in radiomic assessment, and the introduction of personalized targeted approaches will further revolutionize the management of Primary Central Nervous System Lymphoma.

P2, N=68, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2027 --> Dec 2028

P2, N=46, Not yet recruiting, Wake Forest University Health Sciences

P=N/A, N=1000, Recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

The patient initially received 2 cycles of rituximab combined with high-dose methotrexate chemotherapy...Subsequently, the regimen was adjusted to 6 cycles of cytarabine combined with temozolomide chemotherapy followed by radiotherapy for the intracranial lesion...Up to the date of follow-up, the patient's condition was stable without recurrence. Combined with literature review, this article discusses the possible mechanisms of the coexistence of dual-subtype DLBCL (clonal evolution or biclonal origin), the potential pathways of temporal muscle metastasis and the impact of subtype differences on treatment response, which provides clinical reference for the diagnosis and individualized treatment of such rare cases.

Therefore, we upgraded the treatment plan to R-CHOP chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), and achieved a complete remission (CR)...We observe that the combination of HD-MTX and intrathecal chemotherapy exhibits remarkable efficacy in managing post-transplant CNS-PTLD that is resistant to conventional R-CHOP chemotherapy. CAR-T therapy emerges as a potential option for patients suffering from relapsed or refractory CNS-PTLD.