Pb2315: primary central nervous system lymphoma: a retrospective study of the zr or zrm regimen (zanubrutinib, rituximab, methotrexate)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma. Most PCNSL is pathologically classified as diffuse large B-cell lymphoma (DLBCL). High dose systemic methotrexate (HD-MTX) plays an important role in the treatment of PCNSL, but patients cannot tolerate or are not suitable for HD-MTX are often encountered clinically. BTK inhibitors are the recommended second-line option for relapsed refractory cases. In this study, we describe institutional experience with the oral BTK inhibitor Zanubrutinib in combination with rituximab+/- HD-MTX (ZR/ZRM) in patients with central nervous system lymphoma. Aims: To evaluate efficacy and safety of Zanubrutinib, rituximab +/- HD-MTX in patients with primary CNS diffuse large B cell lymphoma. Methods: Zanubrutinib based ZR and ZRM regimen, Zanubrutinib 160mg twice a day, rituximab 375mg/m2 on day 0, MTX 3.5g/ m2 on day 1. After ZR or ZRM induction therapy, CR/CRu/PR patients partially received ASCT or radiotherapy consolidation therapy. Zanubrutinib is used as maintenance therapy, as desired, until the disease progresses. Results: A total of 26 patients with PCNSL were collected from July 1, 2020 to Feb 1, 2023. The median age was 60 years (range 38–76) and eleven were female（42.3%）. The median follow-up time was 19 months (range 3-32), 76.9% patients were treated with Zanubrutinib-containing regimen in the first-line treatment. 12month PFS rate is 45%；12month OS rate is 85%. The ORR in the 26 PCNSL patients was 76.9%, with 8 (30.8%) complete responses (CR) and 12 (46%) partial responses (PR), 4 (15.4%) stable disease (SD) and 2 (7.7%) progressive disease (PD) were observed. 20 patients received first-line treatment with ZR/ZRM, and ORR was 90% (8 CR,10 PR, 2 SD). 6 patients with ZR/ZRM as the second-line or above treatment had an ORR of 33.3% (2 PR, 2 SD, 2PD). Double-expressor lymphoma (DEL) has a shorter PFS than non-double-expressor PCNSL in our research center. The hematological toxicities were quite mild in 16 patients who cannot tolerate HD-MTX and treated with ZR alone. Including thrombocytopenia （Grade 1-2, n=2）, anaemia（Grade 1,n=1）,WBC count decreased（Grade 1,n=1）. It is worth noting that in patients who cannot tolerate high-dose chemoradiotherapy, ZR regimen shows a promising prospect. Summary/Conclusion: This study showed that ZR or ZRM was an effective and safety treatment for PCNSL patients. It is worth noting that in patients who cannot tolerate high-dose chemoradiotherapy, ZR regimen shows a promising prospect.Keywords: Clinical data, CNS lymphoma