Primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL) is a highly aggressive malignancy accounting for over 80% of primary CNS lymphomas, with an annual incidence of 0.4-0.6 per 100,000 people globally and a rising trend in immunocompetent patients. First-line high-dose methotrexate-based chemotherapy causes severe toxicities and nearly 50% of patients relapse within 1-2 years, developing relapsed/refractory (R/R) disease.
Treatment options for R/R PCNSL are scarce, with low response rates, median survival of only 3-6 months, and 5-year survival below 5%. The blood-brain barrier and tumor heterogeneity further worsen outcomes. This prospective, multicenter, single-arm phase II study evaluates the efficacy and safety of pomalidomide, PD-1 inhibitor, and selinexor (PPS) in R/R PCNSL, aiming to provide a new effective treatment.
Histologically confirmed primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL).
Disease progression or relapse after prior treatment with high-dose methotrexate and/or BTK inhibitors.
Age between 18 and 75 years.
ECOG performance status score 0-4.
Presence of another malignant tumor requiring active pharmacological or surgical intervention at present;
Female patients who are pregnant or breastfeeding;
Patients (male or female) of reproductive potential who are unwilling to use or fail to use effective contraceptive measures;
Known hypersensitivity to any study drug or any excipient ingredients of these products;
Single group
Pomalidomide
Drug4 mg on days 1-14, every 3 weeks (q3w), for a total of 6 cycles
PD-1 / PD-L1 monoclonal antibody
Drugtislelizumab 200 mg on day 1, q3w, for a total of 6 cycles
XPO1 inhibitor
DrugSelinexor: 60 mg on days 1, 8, and 15, q3w, for a total of 6 cycles
best overall response rate (ORR) as of 6 cycles of PPS
Overall response rate means sum of complete response rate and partial response rate
Best Complete Response rate (CR) as of 6 cycles of PPS
CR was defined as complete response evaluated using MRI scan
Progression free survival (PFS)
PFS was defined from the date of initiation of PPS to the date fo confirmed disease progression or death of any reason
overall survival (OS)
OS was defined from the date of initiation of PPS to the date fo death
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
measured using CTCAE version 5.0
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