Combination of rituximab and methotrexate followed by rituximab and cytarabine in elderly patients with primary central nervous system lymphoma

The long-term outcomes of PCNSL remains poor which is partially explained by that more than half of patients are diagnosed over the age of 65 years. The optimal treatment strategy for newly diagnosed PCNSL has not been established, especially in the elderly. While the backbone treatment for young patients consist of high-dose methotrexate (MTX) and cytarabine, their feasibility has not been widely tested in the elderly. Moreover, the addition of rituximab has demonstrated inconsistent findings. We have carried out a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in newly-diagnosed PCNLS patients aged ≥60 years. Patients received 5 cycles of MTX (3.5 g/m2) with rituximab (500 mg/m2) every 2 weeks. If CR was not achieved after 5 cycles, 2 additional cycles were applied (total 7 cycles). Patients without progressive disease further received 2 cycles of cytarabine (3000 mg/m2 × 2 days) plus rituximab (500 mg/m2) every 4 weeks. The primary end-point was 2-year progression free survival (PFS) rate, and if 9 or more out of 32 evaluable patients achieved 2-year PFS, the null hypothesis would be rejected. This study was registered at clinicaltrials.gov (NCT03569995). Between Nov. 2018 to November 2020, we enrolled 35 patients from 13 tertiary institutes. The median age was 73 (range 60–81), and 15 patients were male. With 21 (62%) patients were ECOG PS 0–2, 6(17%), 8 (51%), and 11 (31%) patients were categorized as favorable, intermediate, and high-risk group by IELSG classification, respectively. One patient was immediatedly withdrawn because of rapid deterioration, and 34 patients received at least one cycle of induction treatment. Twenty-nine patients completed 5 cycles of induction which resulted in 55% of CR (n = 16) and 41% of PR (n = 12). Twelve patients who had residual disease further received 2 cycles of induction and 3 patients achieved CR (25%) and 7 patients remained in PR. The median dose density of MTX was 100% (range, 65–100). Twenty-six patients proceeded to consolidation treatment, and all could complete it. Among 7 patients who still had residual disease, 4 patiens was converted to CR after consolidation. After a median follow-up duration of 36.0 months (95% CI: 33.2–38.8), 2 year PFS rate was 58.7% (± 9.2%) and 10 patients achieved 2-yr PFS. There was a trend for prolonged PFS for those who achived ≥90% of relative dose intensity of MTX (mPFS 28.8) compared to those who did not (mPFS 13.0). Treatment was generally well-tolerated as only 2 patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. In total of 230 person-cycle, delay of treatment occurred in 21 times. The mOS wasn't reached and the 2-year OS rate was 77.9%. The research was funded by: The Celltrion Inc. provided rituximab (truxima (R)) for in gratis, but was not involved in study analysis. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Chemotherapy, Immunotherapy No conflicts of interests pertinent to the abstract.