Efficacy Analysis of Bruton's Tyrosine Kinase Inhibitor Combined Regimen in the Treatment of Elderly Patients with Relapsed/Refractory Primary Central Nervous System Lymphoma

Background Primary central nervous system lymphoma (PCNSL) is a kind of aggressive non-Hodgkin lymphoma that originates in the brain, spinal cord, eyes or pia mater without evidence of systemic involvement, which accounts for about 3% of central nervous system tumors and has a poor prognosis. Most patients will eventually relapse and the 5-year survival rate is 29.6%. Zanubrutinib is a kind of new generation BTK inhibitor, which can penetrate the blood-brain barrier and be used in the treatment of PCNSL. The study aims to investigate the efficacy and safety of a zanubrutinib-based combination regimen in the treatment of elderly relapsed/refractory(R/R) PCNSL.

Methods We retrospectively analyzed elderly patients with R/R PCNSL who received zanubrutinib-based combination regimen at the Affiliated Hospital of Nantong University over the past few years. We collected the information of patients diagnosed with PCNSL in the SEER project of the National Cancer Institute (NCI), and analyze the survival status. We used CCK8 and EdU to detect the effect of zanubrutinib on the viability and proliferation of activated B-cell subtype (ABC) diffuse large B-cell lymphoma (DLBCL) cell lines with genotypes similar to PCNSL.

Results The 7 elderly R/R PCNSL patients treated with zanubrutinib-based regimen (zanubrutinib, rituximab and temozolomide) showed an overall response rate (ORR) of 85.7% (6/7), a complete response (CR) of 57.1% (4/7) and a partial response (PR) of 28.6% (2/7), and 14.3% (1/7) of patients experienced disease progression (PD). Patients' gender, KPS score, ECOG score, surgical treatment or not, positive cerebrospinal fluid protein (all P>0.05) were not significantly associated with the treatment effect. Pathological type and IESLG score were related to treatment effect (P<0.05). The median progression-free survival (PFS) and median overall survival (OS) of patients in this study were not reached. Through the analysis of clinical data of PCNSL patients in SEER database from 1975 to 2016, it is concluded that elderly patients (age>60 years old) and male PCNSL patients have a worse prognosis, the primary site of PCNSL, treatment methods and the choice of the disease have impact on the prognosis, and there is no significant difference between the disease and other causes in terms of the cause of death. In the survival analysis of elderly patients, gender, surgery and radiotherapy sequence had no significant effect on prognosis, and patients who received chemotherapy had better OS than those who received radiotherapy. The cell viability of ABC subtype DLBCL cell line OCI-Ly10 decreased in a concentration- and time-dependent manner with zanubrutinib and temozolomide (P<0.05). The inhibitory effect of zanubrutinib and temozolomide on the proliferation of OCI-Ly10 cell line was stronger than that of single drug.

Conclusion Zanubrutinib-based combination therapy has good efficacy and controllable safety in elderly R/R PCNSL patients. The prognosis of elderly patients is poor, and the OS of chemotherapy patients is better than that of radiotherapy among the treatment options in the pre-BTKi era. Zanubrutinib inhibits cell viability and cell proliferation in ABC subtype DLBCL cell line OCI-Ly10.

No relevant conflicts of interest to declare.