Abstract Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical
Background: High-dose methotrexate (HD-MTX) is widely used as front-line treatment in patients with primary central nervous system lymphoma (PCNSL). Both preclinical models and clinical data suggested pomalidmide and orelabrutinib were effective in PCNSL and the combination of them may have synergy in DLBCL.
Aims: We aimed to evaluate the tolerability and efficacy of pomalidomide, orelabrutinib and rituximab (POR) with the sequential addition of HD-MTX chemotherapy in newly diagnosed PCNSL.
Methods: This is an investigator-initiated, single-arm phase II study, and immunocompetent patients with untreated PCNSL were enrolled.
Patients were treated with pomalidomide 4mg once per day on days 1-14, orelabrutinib 150 mg once daily continuously, and rituximab 375 mg/m2 intravenous once on day 1 of each 21-day cycle. After four cycles, HD-MTX chemotherapy was sequentially added for two additional cycles. The primary endpoint was overall response rate (ORR) at the end of four cycles of POR. Circulating tumor DNA detection of cerebrospinal fluid was performed. This trial was registered at www.clinicaltrials.gov (#NCT 05390749).
Results: The data cut-off date was 15th Feb 2023, and thirteen patients were enrolled in this study. The median age was 58 years (range, 34-79 years). Four patients had eye involvement and one patient had leptomeninges involvement. Eight patients performed ctDNA analysis and all had MYD88 l265p mutation. One patient discontinued the experimental treatment due to treatment-related adverse events (TRAE) and eleven patients finished four cycles of POR and were evaluable. The ORR after four cycles of POR was 90.1% and the complete response rate was 36.4%. Twelve patients who finished at least 1 cycle were evaluated for safety analysis. The most common grade 3 or 4 AEs were neutropenia (G3,n=1; G4, n=2), thrombocytopenia (G3, n=2), rash(G3 n=1, G4 n=1), ALT increased (G3, n=1) and anemia(G3,n=1). With a median follow-up of 4 months, one patient relapsed and died of PCNSL.
Summary/Conclusion: This is the first study to treat newly diagnosed PCNSL with a targeted therapy combination before chemotherapy. POR produced a high ORR with good tolerance. This suggested the potential of noncytotoxic first-line therapies for PCNSL.
Funding:
CAMS Innovation Fund for Medical Sciences（CIFMS）2021-I2M-C&T-B-005.
*Corresponding author
Dao-bin Zhou
Address: Shuaifuyuan No. 1, Dongcheng District, Beijing, China.
Tel: +86 13901113623
Keywords: Lymphoma therapy, Non-Hodgkin’s lymphoma, CNS lymphoma