Blood brain barrier disruption (BBBD) and intra-arterial methotrexate based therapy for newly diagnosed primary CNS lymphoma: The BBBD Consortium Experience

Abstract

2014 Background: Primary central nervous system lymphoma (PCNSL) incidence in immunocompetent patients has been increasing and now represents 4% of intracranial neoplasms. Similar to systemic lymphoma, PCNSL can display considerable chemosensitivity. Most chemotherapy regimens for PCNSL use intravenous methotrexate, often in combination with whole brain radiation. We present our multi- institutional experience in the treatment of PCNSL using BBBD in conjunction with Intra-arterial methotrexate (IA MTX)-based chemotherapy. Methods: A retrospective IRB approved analysis was performed on 177 newly diagnosed PCNSL patients treated monthly with osmotic BBBD in conjunction with an IA MTX-based chemotherapy regimen (n= 2,469 procedures) at 4 institutions from 1982–2005. No patient had received prior irradiation. Descriptive summaries and Kaplan-Meier survival summaries were estimated. Results: Among 177 patients, median age at diagnosis was 59.1 years (range 5.7 to 82.7 years). 101 patients (57%) achieved a complete response and 41 (23%) achieved a partial response (overall response rate 80.2%). 67 patients (37%) are currently alive (57 [32%] with no evidence of disease). Median overall survival (OS) was 3.1 years (25% estimated survival at 11.3 years). Median progression free survival (PFS) was 1.6 years with 40% progression-free at 5 years. Evaluation of the subgroup of patients < 60 years (n= 100), demonstrated an OS of 5.2 years with a 40% survival plateau after about 8 years, suggesting that some of these patients may be cured. The procedures were generally well tolerated with the most frequently encountered complication being procedure related seizures (9.5%) without long-term sequelae. Conclusions: This large multi-center series demonstrates that BBBD/IA MTX is a generally well tolerated and effective treatment for patients with newly diagnosed PCNSL. Further, it allows for the deferral of radiation and its associated cognitive compromise in these patients. These results are comparable or superior to other published chemotherapy (± radiation) treatment regimens suggesting that BBBD/IA MTX is an excellent treatment option for PCNSL patients and can result in successful and durable tumor control. No significant financial relationships to disclose.