HDMTX-based polychemotherapy including intraventricular therapy in elderly patients with primary CNS lymphoma: a single center series

Abstract

Background: To investigate outcome and toxicity of high-dose systemic methotrexate (HDMTX)-based polychemotherapy and intracerebroventricular (ICV) chemotherapy via an Ommaya reservoir in elderly patients with primary central nervous system lymphoma (PCNSL). Methods: We performed a retrospective analysis on patients ⩾65 years with first diagnosis of PCNSL admitted to our center between January 2015 and December 2019. These patients were treated with a standardized chemotherapy protocol in case of absent contraindications for HDMTX-based chemotherapy. The protocol contained induction therapy with systemic rituximab, methotrexate and ifosfamide and consolidation treatment with systemic cytarabine (AraC) and ICV methotrexate, prednisolone and AraC. Results: Of a total of 46 patients seen in this period, 3 did not qualify for HDMTX. Thus, 43 patients were included in this analysis. Median age was 74 years (range 65–86), median Karnofsky performance score was 50 (range 20–90). Of the 43 patients, 32 (74.4%) completed treatment including ICV therapy. Complete remission/complete remission unconfirmed was achieved in 26 of 43 patients (60.5%), partial response (PR) in 3 (7%); 5 (11.6%) had progressive disease, and 3 (7.0%) died due to treatment-related complications; in the remaining 6 (14.0%) therapy could not be completed. Median progression free survival was 16 months (95% confidence interval 8–24 months) and median overall survival had not been reached after a median follow up of 23 months (range 1–52 months); the 75th percentile survival time was 12 months. No Ommaya reservoir infection was observed. Complications of ICV treatment were pericatheter leucencephalopathy in two patients and surgical scar dehiscence with cerebrospinal fluid leak in one patient. Conclusion: Toxicity of HDMTX plus ICV chemotherapy for elderly patients with PCNSL was manageable and outcome was excellent for patients treated with this protocol.

Ibrutinib Monotherapy as Bridge-to-Transplant for Relapsed/Refractory Primary Oculo-Cerebral Lymphoma

“…Data regarding surgical treatment of PCNSLs is scarce. Previously published data agree that resection is discouraged [ 21 , 22 , 23 ].…”

Primary central nervous system lymphoma (PCNSL) in older patients

“…In a retrospective study, Seigel et al reported a 60.5% CR rate and a median PFS of 16 months (8–24 months) in 46 patients ≥ 65 years treated with HD-MTX/ifosfamide/AraC as systemic therapy associated with IT injection of MTX with prednisolone and AraC. Toxicity was manageable [55 ▪ ]. Another retrospective study including 19 patients > 80 years, showed the feasibility of HD-MTX polychemotherapy in this population, with a median OS of 16.3 months [56].…”

“…However, particularly in the elderly population, the risk-benefit balance is not clearly established between a potential improvement of PCNSL response versus the risk of an increase of immunosuppression. The phase 3, HOVON trial explored the M ethotrexate, BCNU, etoposide, Prednisone (MBVP) protocol with (n ¼ 99) or without rituximab (n ¼ 100), median age was 61 (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). We only observed a trend in favor of rituximab, PFS at 1 years was 58% and 65% (P ¼ 0.18) and median OS was 56.7 months and not reached (P ¼ 0Á74) for R-MBVP and MBVP respectively [53].…”

Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

“…HD-MTX penetrates the meninges well and the use of intrathecal treatment (MTX and cytarabine) in patients with lymphomatous meningitis treated with HD-MTX has not been established in the absence of controlled trials. If used, these drugs are likely delivered through an intraventricular Ommaya reservoir with a reservoir infection rate of 9% [ 68 ]. This approach was proposed in some chemotherapy regimens, including those used with elderly patients [ 9 , 68 , 69 , 70 ], and may be discussed when intravenous MTX is administered at doses below 3 g/m 2 , to allow reaching cytotoxic levels in the CSF.…”

“…If used, these drugs are likely delivered through an intraventricular Ommaya reservoir with a reservoir infection rate of 9% [ 68 ]. This approach was proposed in some chemotherapy regimens, including those used with elderly patients [ 9 , 68 , 69 , 70 ], and may be discussed when intravenous MTX is administered at doses below 3 g/m 2 , to allow reaching cytotoxic levels in the CSF.…”