Relapsed Primary Central Nervous System Lymphoma: Current Advances.
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ABSTRACT:
SUBMITTER: Tao K
PROVIDER: S-EPMC8118624 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Opinion statementTherapeutic options are limited in primary central nervous system lymphoma (PCNSL) with no uniform consensus on optimal management and few published, randomized trials. High-dose methotrexate in combination with other chemotherapeutic agents forms the mainstay of treatment. There hasn't been much progress beyond high-dose methotrexate in this disease, and although results from trials using high-dose chemotherapy and autologous stem-cell transplant seem promising, these need to be further validated. Moreover, the role of whole brain radiation in the upfront setting remains to be determined. However, international efforts in this direction are underway, with ongoing randomized trials in newly diagnosed PCNSL, more research on the molecular pathogenesis and biomarkers, and the use of novel agents in salvage therapy. There also is emphasis on quality of life parameters and neurocognitive status. Future treatment options should optimize high-efficacy rates while minimizing the risk of neurotoxicity.
| S-EPMC3841579 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma primarily involving the brain, spinal cord, or leptomeninges. PCNSL is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation has improved the survival outcome, together with reduced neurotoxicity. Recent studies found that aberrant activation of the B-cell receptor-signaling pathway and activation of the NF-?B are frequent genetic alterations and could be good targets for the treatment of PCNSL. Herein, we have reviewed the current status and recent advances in the biology and management of PCNSL.
| S-EPMC7386887 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) is a group of extranodal non-Hodgkin lymphoma that exhibits specific biological characteristics and clinical behavior, with an aggressive disease course and unsatisfactory patient outcomes. It is of great importance to identify aberrant genetic loci and important molecular pathways that might suggest potential targets for new therapeutics and provide prognostic information. In this review, we listed various genetic and epigenetic alterations that are involved in PCNSL pathogenesis. In the aspect of treatment, we summarized the related literatures and evaluated the efficacy of surgery, induction chemotherapy, radiotherapy, intrathecal chemotherapy, and autologous stem cell transplantation in PCNSL. We also proposed the possible new agents for recurrent and relapse PCNSL based on the result of recent clinical researches.
| S-EPMC6371000 | biostudies-literature
Project description: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.
| S-EPMC8101140 | biostudies-literature
Project description:BACKGROUND: Lenalidomide is an immunomodulator agent that exhibits efficacy in multiple myeloma and haematological malignancies including refractory/relapsed diffuse large B-cell (DLBC) systemic lymphoma. METHODS: Retrospective review of PCNSL patients treated with lenalidomide at the Pitié-Salpêtrière hospital. Inclusion criteria were: 1) immunocompetent status 2) pathologically proven diagnosis of DLBC-PCNSL, 3) recurrent or refractory disease after at least two prior chemotherapy treatments, including intravenous high-dose methotrexate and cytarabine based regimens, 4) lenalidomide administered orally, at a dose of 25 mg/day on days 1-21 of a 28-days cycle. MRI scans were performed monthly. Response was evaluated according to the IPCG criteria. RESULTS: Between June 2011 and March 2013, 6 patients (4 women and 2 men) met the inclusion criteria. Lenalidomide was given as 3rd line in four patients, as 4th line in one and 5th line in one. Median age was 73.5 years (range 64-78) and median Karnofsky Performance Status was 60 (range 40-70). Two patients achieved complete response (CR). Patient 1 received a total of 9 monthly cycles of lenalidomide without any steroids and is still in remission after a follow-up of 18 months from the start of the treatment. Patient 2 achieved a CR and was off-steroids at the time of CR, but relapsed during the 3rd cycle and died after 14 weeks. Patient 3 achieved a partial response after one cycle but died suddenly during the 2nd cycle. Patients 4, 5 and 6 progressed and died 2, 5 and 6 months respectively after the start of lenalidomide. One of them who suffered from an oculo-cerebral relapse demonstrated a partial ocular response while progressing in the brain. Apart from the sudden death of unknown cause, the treatment was well tolerated. None of the patients experienced any grade III or IV toxicity. CONCLUSIONS: These results suggest that lenalidomide exhibits activity in heavily pre-treated PCNSL and is well tolerated in elderly patients. Lenalidomide efficacy on PCNSL needs to be evaluated prospectively, alone or in association with other cytotoxic agents. A phase II trial combining rituximab and lenalidomide for recurrent PCNSL is on-going in France (NCT01956695).
| S-EPMC4185581 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma (NHL) confined to the brain, leptomeninges, eyes, or spinal cord. The majority of PCNSL cases occur in the immunocompetent host, the focus of this review. The prognosis of PCNSL is inferior to that of other NHL subtypes including other organ-specific subtypes of extranodal NHL. The 5- and 10-year survival proportions for PCNSL are 29.3% and 21.6%, respectively. The diagnosis and management of PCNSL differs from that of other primary brain cancers and NHL in other parts of the body.
| S-EPMC6142465 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or vitreoretinal space, without evidence of systemic involvement. The diagnosis of PCNSL requires a high level of suspicion because clinical presentation varies depending upon involved structures. Initiation of treatment is time sensitive for optimal neurologic recovery and disease control. In general, the prognosis of PCNSL has improved significantly over the past few decades, largely as a result of the introduction and widespread use of high-dose methotrexate (MTX) chemotherapy, which is considered the backbone of first-line polychemotherapy treatment. Upon completion of MTX-based treatment, a consolidation strategy is often required to prolong duration of response. Consolidation can consist of radiation, maintenance therapy, nonmyeloablative chemotherapy, or myeloablative treatment followed by autologous stem cell transplant. Unfortunately, even with consolidation, relapse is common, and 5-year survival rates stand at only 30% to 40%. Novel insights into the pathophysiology of PCNSL have identified key mechanisms in tumor pathogenesis, including activation of the B-cell receptor pathway, immune evasion, and a suppressed tumor immune microenvironment. These insights have led to the identification of novel small molecules targeting these aberrant pathways. The Bruton tyrosine kinase inhibitor ibrutinib and immunomodulatory drugs (lenalidomide or pomalidomide) have shown promising clinical response rates for relapsed/refractory PCNSL and are increasingly used for the treatment of recurrent disease. This review provides a discussion of the clinical presentation of PCNSL, the approach to work-up and staging, and an overview of recent advancements in the understanding of the pathophysiology and current treatment strategies for immunocompetent patients.
| S-EPMC9437714 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL), confined to the brain, eyes, spinal cord or leptomeninges without systemic involvement. Overall prognosis, diagnosis and management of PCNSL differ from other types of NHL. Prompt diagnosis and initiation of treatment are vital to improving clinical outcomes. PCNSL is responsive to radiation therapy, however whole-brain radiotherapy (WBRT) inadequately controls the disease when used alone and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients. High-dose methotrexate (HD-MTX)-based induction chemotherapy with or without autologous stem cell transplantation (ASCT) or reduced-dose WBRT leads to durable disease control and less neurotoxicity. The optimal treatment has yet to be defined, however HD-MTX-based induction chemotherapy is considered standard for newly diagnosed PCNSL. Ongoing randomized trials address the role of rituximab, and of consolidative treatment using ASCT or reduced-dose WBRT. Despite high tumor response rates to initial treatment, many patients have relapsing disease with very poor prognosis. The optimal treatment for refractory or relapsed PCNSL is poorly defined. The choice of salvage treatment depends on age, previous treatment and response, performance status and comorbidities at the time of relapse. Novel therapeutics targeting underlying tumor biology include small molecule inhibitors of B-cell receptor, cereblon, and mammalian target of rapamycin signaling, and immunotherapy programmed cell death 1 receptor inhibitors and chimeric antigen receptor T cells.
| S-EPMC6174646 | biostudies-literature
Project description:Background and objectivePrimary central nervous system lymphoma (PCNSL) is a rare and highly invasive non-Hodgkin lymphoma that is challenging to diagnose and treat. It is typically confined to the brain, spinal cord, and eyes. The diagnosis of PCNSL lacks specificity, and the misdiagnosis and missed diagnosis rates of PCNSL are high. Traditional treatments for PCNSL, such as surgery, whole-brain radiation therapy, high-dose methotrexate-based chemotherapy, and rituximab (RTX), have been associated with higher initial remission rates. However, the duration of any remission is short, the recurrence rate is high, and treatment-related neurotoxicity is strong, which are challenges for medical researchers. This review provides an overview of and perspectives on the diagnosis, treatment, and evaluation of patients with PCNSL.MethodsThe PubMed database was searched to retrieve articles published from January 1, 1991, to June 2, 2022 using the following Medical Subject Headings (MeSH) terms: "Primary central nervous system lymphoma" and "clinical trial". The American Society of Clinical Oncology and the National Comprehensive Cancer Network guidelines were also reviewed to obtain additional information. The search was limited to articles published in English, German, and French. In total, 126 articles were deemed eligible for inclusion in this study.Key content and findingsIn terms of the diagnosis of PCNSL, a combination of flow cytometry and cytology has been shown to improve the diagnostic accuracy of PCNSL. Additionally, interleukin 10 and chemokine C-X-C motif ligand 13 are promising biomarkers. In terms of the treatment of PCNSL, programmed death-1 (PD-1) blockage and chimeric antigen receptor T cell (CAR-T) therapy treatments have shown prospective efficacy, but more clinical trials need to be conducted to gather further evidence. We also reviewed and summarized prospective clinical trials on PCNSL.ConclusionsPCNSL is a rare and highly aggressive lymphoma. The treatment of PCNSL has progressed significantly, and while the survival of patients has improved, relapse and low long-term survival remain huge challenges. Continuous in-depth research is being conducted on new drug therapies and combination therapies for PCNSL. A combination of targeted drugs (e.g., ibrutinib, lenalidomide, and PD-1 monoclonal antibody) and traditional therapy represents the main research direction for future PCNSL treatments. CAR-T has also shown great potential in the treatment of PCNSL. With the development of these new diagnostic and therapeutic methods and further research into the molecular biology of PCNSL, patients with PCNSL should achieve a better prognosis.
| S-EPMC10248585 | biostudies-literature
Project description:Purpose of reviewPrimary central nervous system lymphoma (PCNSL) is an aggressive malignancy confined to the brain, spinal cord, leptomeninges, and eyes. Due to its rarity, there is a paucity of randomized trials and a varied approach to its management in the oncologic community. This review summarizes recent literature guiding current clinical practice.Recent findingsThe presentation, work up, and management of PCNSL are discussed. Induction therapy incorporates a methotrexate-based chemotherapy regimen and is generally followed by a consolidation regimen including high dose chemotherapy (with or without autologous stem cell rescue). Whole brain radiation therapy (WBRT) is a potential additional consolidation strategy. Management of relapsed and refractory disease poses a special challenge due to poor outcomes. Immunotherapy and targeted treatments are promising novel strategies for recurrent/refractory patients. Currently, there is little consensus in the management of PCNSL. Treatment recommendations should be tailored to the individual patient, with consideration for risk of neurotoxicity. New, exciting strategies are in development and when feasible, enrollment in a clinical trial should be considered.
| S-EPMC6636316 | biostudies-literature