ML-15 The future direction of treatment development for primary central nervous system lymphoma (PCNSL)

Abstract Purpose: We found that the combination of high-dose Methotrexate (HD-MTX)-based therapy and histone deacetylase inhibitor (HDACI) had a therapeutic effect on PCNSL. In addition, this year, tirabrutinib, a Bruton’s tyrosine kinase inhibitor, was approved for marketing as a single agent for relapsed/refractory PCNSL, and new therapeutic development is expected. We will examine the treatment results of PCNSL in our department retrospectively and discuss the future direction of treatment development. METHODS: From 2001 to 2014, 82 newly diagnosed PCNSL patients treated with HD-MTX/Procarbazine (MP) as initial remission induction chemotherapy were retrospectively analyzed. RESULTS: Complete response (CR) was obtained in 38 patients (46.3%) after initial chemotherapy, and the median overall survival (OS) in the CR and non-CR groups was 2636 days and 728 days, respectively, and significantly shorter in the non-CR group (p<0.01). In the CR group, 27 cases (71.1%) recurred and 12 cases received HD-MTX re-challenge (M-re), 14 cases received treatment other than M-re (1 case did not receive treatment), the median OS after relapse was 590 days. The median post-relapse progression-free survival (PFS) of the 10 patients undergoing M-re at the first relapse was 116 days, the median OS after relapse was 590 days. The median post-relapse PFS of 16 patients receiving other treatments was 428 days, the median OS after relapse was 532 days. There was no difference in PFS and OS after recurrence in treatment at the first recurrence (p=0.15, p=0.55). Conclusion: The OS of non-CR patients in the initial chemotherapy and the OS after recurrence after CR were short. The possible directions of PCNSL treatment development include 1) increasing the CR rate with initial chemotherapy and maintaining CR for a long time for newly diagnosed PCNSL, and 2) finding an effective treatment for recurrence. New drugs such as tirabrutinib and HDACIs may be breakthroughs.