Current and emerging therapies for primary central nervous system lymphoma

Abstract

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Targeted agents against the B-cell receptor signaling pathway, microenvironment immunomodulation and blood-brain barrier (BBB) permeabilization appear to be promising in treating refractory/relapsed patients. Chimeric antigen receptor-T cells (CAR-T cells) have been shown to penetrate the BBB as a potential tool to manipulate this disease entity while controlling CAR-T cell-related encephalopathy syndrome. Future approaches may stratify patients according to age, performance status, molecular biomarkers and cellular bioinformation. This review summarizes the current therapies and emerging agents in clinical development for PCNSL treatment.

Use of rituximab, temozolomide, and radiation in recurrent and refractory primary central nervous system lymphoma in the Philippines: a retrospective analysis

“…In the NCCN guidelines, the options for such patients include systemic chemotherapy, radiotherapy with or without chemotherapy, or high-dose MTX therapy with stem cell rescue. 8 …”

“…High-dose methotrexate, other systemic chemotherapy, and stem cell therapy are also considered options. 8 …”

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

“…Based on the limited number of studies, dose-reduced WBRT seems to be less toxic than non-reduced dose WBRT in terms of neurologic functional impairment [71,72], and demonstrated a similar response to ASCT [73]. Currently, up to 36 Gy of WBRT with a boost to gross disease to a total of 45 Gy is recommended to the patients who achieve less than CR in systemic induction therapy [1,74].Therefore, for PCNSL patients who get CR/CRu but cannot tolerate ASCT treatment, dosereduced WBRT (< 23.4 Gy) can be considered as one of the consolidation therapeutic strategies, given the balance of neurotoxicity and treatment effectiveness [74]. However, there is no study directly comparing dosereduced WBRT and ASCT on treatment effect and AEs.…”

“…Primary central nervous system lymphoma (PCNSL) is one type of extra-nodal non-Hodgkin lymphoma (NHL), where involvement is restricted to the brain, spinal cord, cranial nerves, leptomeninges and vitreo-retina [1,2]. It is a relatively rare tumor, accounting for about 1% of NHLs and 3-4% of intracranial tumors [3].…”

Role of Positron Emission Tomography in Primary Central Nervous System Lymphoma

“…Recently, other biological factors or molecular characteristics of tumors have been identified. For example, it has been reported that high protein levels of interleukin (IL)-10 at diagnosis or co-expression of MYC/BCL2 in tumors correlate with low overall survival (OS) and progression-free survival (PFS) [ 56 , 57 ]. In addition, many prognostic factors have been proposed in MRI, including multifocal lesions, high tumor volume, or subtentorial involvement, but with controversial results [ 58 , 59 ].…”