A phase 2 study of ibrutinib maintenance following first‐line high‐dose methotrexate‐based chemotherapy for elderly patients with primary central nervous system lymphoma

Abstract

BackgroundElderly 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.MethodsThis 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.ResultsTwenty 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%.ConclusionsThe 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.

Prolonged remission with ibrutinib maintenance therapy following radiation in a patient with relapsed primary CNS lymphoma

“…The proposal to use ibrutinib as maintenance therapy following salvage WBRT in the treatment of r/r PCNSL to extend the duration of response to the anti-lymphoma treatment is supported by prior literature studies in which single-agent ibrutinib demonstrated safety and efficacy in the treatment of newly diagnosed PCNSL as maintenance therapy [ 10 ] and in the treatment of some r/r PCNSL cases [ 21 , 22 ]. In one phase II study involving 29 r/r PCNSL and 15 secondary CNS lymphoma cases, treatment using single-agent ibrutinib resulted in an overall response rate of 78%, a median progression-free survival (PFS) of 4 months, and a median OS of 19.5 months [ 22 ].…”

“…Nonstandard consolidation therapy options for PCNSL include high-dose systemic chemotherapy with autologous stem-cell rescue; traditional chemotherapy such as cytarabine + thiotepa followed by carmustine + thiotepa, thiotepa, busulfan, and cyclophosphamide; high dose cytarabine + etoposide; and high-dose cytarabine [ 7 ] and half-dose whole-brain radiation therapy (WBRT) [ 8 ]. Nonstandard maintenance therapy options for PCNSL include monthly HD-MTX, temozolomide, rituximab, lenalidomide, procarbazine, and ibrutinib [ 7 , 9 , 10 ]. More attention has recently been drawn to maintenance therapy to prolong the duration of remission achieved by induction therapy, particularly in the elderly who cannot tolerate consolidation therapies [ 9 ].…”