Introduction：PCNSL is a diffuse large B cell lymphoma (DLBCL) occurring exclusively in the brain, spinal cord, cranial nerves, leptomeninges and/or eyes. Pathophysiology is incompletely understood, although a central role seems to comprise immunoglobulins binding to self-proteins expressed in the central nervous system (CNS) and alterations of genes involved in B cell receptor, Toll-like receptor and NF-κB signalling. Standard of care includes methotrexate-based polychemotherapy followed by age-tailored thiotepa-based conditioned autologous stem cell transplantation, whole-brain radiotherapy or singledrug maintenance。Lenalidomide, an immunomodulatory agent that penetrates the CNS, has shown promise in relapsed/refractory (R/R) aggressive NHL, with well-demonstrated singleagent activity and tolerability. We hypothesized that lenalidomide combined with immunochemotherapy(MTX-based regimen)might be a favorable option for PCNSL pts. Here, we present preliminary data from the phase 2 trial of lenalidomide combined with immunochemotherapy in PCNSL pts (NCT04737889).

To investigate the efficacy of lenalidomide combined with immunochemotherapy in untreated PCNSL.The primary objective is 2-year progression free survival(PFS). The secondary objectives are objective response rate (ORR), incidence of grade 3/4 adverse event (AE), and overall survival (OS).

aged 18-75 years untreated PCNSL and adequate organ function are being enrolled.Lenalidomide(25mg qd po,totally 10 days/cycle) plus R-MT(Rituximab-Methotrexate+Temozolomide) was administered in TN PCNSL. A totally of 6 cycles of treatment was planned for pts. Completed responders(CR) undergo autologous stem cell transplantation (ASCT) 、reduced dose whole brain radiotherapy or lenalidomide maintenance for 24 months, based on the patient's fitness and preference.

RESULTS：From March 2019 to 18 April 2023, 24 pts have been enrolled . Their baseline characteristics are displayed in Table 1.

By 30 May 2025, all pts had been evaluated for response. There were 19 CRs (79.2%), 3 PRs (12.5%) and 2 PDs(8.3%) . The median follow-up time was10 (1.2 - 51.4) months . One pt withdrew informed consent due to grade 3 renal toxicity , One died from non-tumor-related disease. Two year progression-free survival (PFS) and overall survival was 62% and 67%，respectively,the median PFS and OS not achieved.

The most common adverse events were hematologic toxicities. Grade 3/4 AEs occurred in ≥20% pts were neutropenia, leukopenia .Grade 3/4 non-hematologic AEs occurred in ≥20% pts was hepatic injury.

Lenalidomide combined with immunochemotherapy showed encouraging activity and acceptable tolerance in pts with TN PCNSL.The study is still ongoing and it is worth looking forward to updating the long-term survival data.

No relevant conflicts of interest to declare.

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2023
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