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Background: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression‐free survival (PFS) of 6–16 months. Ibrutinib penetrates the blood–brain barrier and has shown activity in PCNSL. Methods: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2‐year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60–85 years old who responded to first‐line high‐dose methotrexate (HDMTX)‐based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity. Results: Twenty patients were enrolled, with a median age of 72 years (range, 61–80). Median time on ibrutinib maintenance was 12.5 (range, 2–46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1‐ and 2‐year PFS are 90% and 72.6%, respectively, and the 2‐year OS is 89%. Conclusions: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly. Ibrutinib maintenance following first‐line high dose methotrexate‐based chemotherapy in elderly patients with primary central nervous system lymphoma is feasible and probably also effective. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare disease with an incidence of 0.4/per 100,000 person‐years. As there is a limited number of prospective randomized trials in PCNSL, large retrospective studies on this rare disease may yield information that might prove useful for the future design of randomized clinical trials. We retrospectively analyzed the data of 222 newly diagnosed PCNSL patients treated in five referral centers in Israel between 2001 and 2020. During this period, combination therapy became the treatment of choice, rituximab has been added to the induction therapy, and consolidation with irradiation was largely laid off and was mostly replaced by high‐dose chemotherapy with or without autologous stem cell transplantation (HDC‐ASCT). Patients older than 60 comprised 67.5% of the study population. First‐line treatment included high‐dose methotrexate (HD‐MTX) in 94% of patients with a median MTX dose of 3.5 g/m2 (range 1.14–6 g/m2) and a median cycle number of 5 (range 1–16). Rituximab was given to 136 patients (61%) and consolidation treatment to 124 patients (58%). Patients treated after 2012 received significantly more treatment with HD‐MTX and rituximab, more consolidation treatments, and autologous stem cell transplantation. The overall response rate was 85% and the complete response (CR)/unconfirmed CR rate was 62.1%. After a median follow‐up of 24 months, the median progression‐free survival (PFS) and overall survival (OS) were 21.9 and 43.5 months respectively with a significant improvement since 2012 (PFS: 12.5 vs. 34.2 p = 0.006 and OS: 19.9 vs. 77.3 p = 0.0003). A multivariate analysis found that the most important factors related to OS were obtaining a CR followed by rituximab treatment and Eastern Cooperative Oncology Group performance status. The observed improvement in outcomes may be due to multiple components such as an intention to treat all patients regardless of age with HD‐MTX‐based combination chemotherapy, treatment in dedicated centers, and more aggressive consolidation with the introduction of HDC‐ASCT. [ABSTRACT FROM AUTHOR]