ML-02 Chemotherapy for patients with relapsed or refractory primary CNS lymphoma

BACKGROUNDS: Standard of care for patients with primary CNS lymphoma (PCNSL) has been high-dose methotrexate (HD-MTX)-based multiagent immunochemotherapy, particularly with R-MPV-A with or without whole-brain radiotherapy (WBRT), however, the optimal treatment for relapsed/refractory (r/r)PCNSL has not been established yet. Approval of a second-generation BTK inhibitor, tirabrutinib, for r/rPCNSL in Japan in March 2020, prompted us to evaluate retrospectively efficacy of R-MPV-A for r/rPCNSL to compare their activities. PATIENTS: Histologically proven PCNSL patients treated at relapse in our institution from April 2000 to November 2019 were analyzed. Outcomes were compared between those treated with RMPVA or other regimens. RESULTS: Among 148 PCNSL patients identified, 73 had at least one relapse, of whom 47 received salvage chemotherapy including 23 treated with RMPVA, 14 with HD-MTX monotherapy, and 11 with DeVIC (DEX, etoposide, ifosfamide, CDBCA). Median age/KPS were 69 yo (20–87)/ 80 (40–100), 27 patients had received prior WBRT. RMPVA was given at the first relapse in 11 patients, median number of RMPV cycles was 8 (1–4 cycles: 10; 8 cycles 13). CR/CRu were achieved in 19 (83%), response rate was 87%, while there were two PDs (9%). After median follow-up of 21.9 months, the median PFS after salvage RMPVA was 13.0 m (95%CI: 9.1–16.9), 1-year overall survival (OS) was 82%, median OS was 70.0 m (95%CI: 12.9–127.1), which were longer than those in 24 patients with salvage treatment other than RMPVA (mPFS 4.4 m, P=0.054; mOS 13.6 m, P=0.009). Median PFS and OS for HD-MTX monotherapy were 5.1m and 36.6 m, while those for DeVIC were 4.4 m and 9.1 m, respectively. Treatment was generally well-tolerated but there was one treatment-related death. CONCLUSIONS: Salvage RMPVA at relapses was active and associated with longer survival compared with other regimens, necessitating further development of salvage regimens incorporating tirabrutinib in the future studies.