Advances and challenges in the treatment of primary central nervous system lymphoma

Abstract

Primary central nervous system lymphoma (PCNSL), a rare variant of non‐Hodgkin's lymphoma, is characterized by distinct biological characteristics and clinical behaviors, and patient prognosis is not satisfactory. The advent of high‐dose (HD) methotrexate (HD‐MTX) therapy has significantly improved PCNSL prognosis. Currently, HD‐MTX‐based chemotherapy regimens are recognized as first‐line treatment. PCNSL is sensitive to radiotherapy, and whole‐brain radiotherapy (WBRT) can consolidate response to chemotherapy; however, WBRT‐associated delayed neurotoxicity leads to neurocognitive impairment, especially in elderly patients. Other effective approaches include rituximab, temozolomide, and autologous stem‐cell transplantation (ASCT). In addition, new drugs against PCNSL such as those targeting the B‐cell receptor signaling pathway, are undergoing clinical trials. However, optimal therapeutic approaches in PCNSL remain undefined. This review provides an overview of advances in surgical approaches, induction chemotherapy, radiotherapy, ASCT, salvage treatments, and novel therapeutic approaches in immunocompetent patients with PCNSL in the past 5 years. Additionally, therapeutic progress in elderly patients and in those with relapsed/refractory PCNSL is also summarized based on the outcomes of recent clinical studies.

Successful Treatment of Primary CNS Extranodal NK/T-Cell Lymphoma with Surgery and Chemotherapy Combined with Sintilimab: A Case Report and Literature Review

“…Currently, the standardized therapeutic strategy for CNS lymphoma includes radiation therapy and high-dose MTX. 29 The use of whole brain radiation therapy (WBRT) in PCNSL treatment is controversial, especially in patients over 60 years of age, due to its limited efficacy and late-onset neurotoxicity. 1 In our case, the patient underwent surgical excision and was received six cycles of PD1 monoclonal antibody (Sintilimab), high-dose methotrexate, pegaspargase, thiotepa chemotherapy regimen plus intrathecal chemotherapy.…”

“…Due to the short survival period of standard treatment and the highly aggressive course of this tumor, some clinicians recommend bone marrow or peripheral stem cell transplantation to consolidate. 29 Nonetheless, there are no reliable data for NK/T-cell lymphoma, and this treatment strategy is usually used for the treatment of B-cell lymphoma. Due to the difficulty in performing clinical trials for PCNS ENK/T-cell lymphoma, there is still a lack of standardized treatments.…”

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

“…These accounts for 3.3% of intracranial tumors, and because of the low incidence and limited drug options, efficient treatment is limited. Overall survival (OS) rate in patients with PCNSL and long-term survival is much lower than the same histological type of lymphoma involving peripheral lymphoid organs [ 15 , 16 , 17 ]. PCNSL appears frequently among elderly or immunocompromised (HIV/AIDS-acquired immune deficiency syndrome, organ transplant, immunosuppressive agents) patients.…”

Epidemiologic Characteristics, Prognostic Factors and Treatment Outcomes in Primary Central Nervous System Lymphoma: A SEER-Based Study

“…However, WBRT-associated delayed neurotoxicity has limited its use, especially for age older than 60 years [7,22,23]. Given the higher risk of neurotoxicity and the limited durability of treatment responses, WBRT is not considered as the standard initial therapy for PCNSL patients [24,25]. Recently, many clinical studies have engaged in whether different radiotherapy regimens (including reduced-dose and partial-brain radiotherapy) combination with chemotherapy can bring better clinical outcomes [26][27][28][29][30].…”