Treatment approaches for primary CNS lymphomas

Carrabba, Matteo Giovanni; Reni, Michele; Foppoli, Marco; Chiara, A.; Franzin, Alberto; Politi, Letterio S.; Villa, Eugenio; Ciceri, Fabio; Ferreri, Andrés J.M.

doi:10.1517/14656561003767456

Cited by 16 publications

(6 citation statements)

References 76 publications

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“…Some consider a combination of methotrexate and cytarabine as the treatment standard [36, Class IV]. Rituximab alone or in combination with other therapies has also been suggested [37, 38], particularly, in relapsed or recurrent disease [39, Class IV].…”

Section: Treatmentmentioning

confidence: 99%

Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

Nath

Berger

2012

Curr Treat Options Neurol

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Opinion statement The first critical step in the appropriate treatment of neurological infectious disease accompanying immunosuppressive states or immunomodulatory medication is to properly identify the offending organism. Broadly immunosuppressive conditions will predispose to both common and uncommon infectious diseases. There are substantial differences between neurological infectious disorders complicating disturbances of the innate immunity (neutrophils, monocytes and macrophages) and those due to abnormal adaptive immunity (humoral and cellular immunity). Similarly, there are differences in the types of infections with impaired humoral immunity compared to disturbed cellular immunity and between T- and B-cell disorders. HIV/AIDS has been a model of acquired immunosuppression and the nature of opportunistic infections with which it has been associated has been well characterized and generally correlates well with the degree of CD4 lymphopenia. Increasingly, immunotherapies target specific components of the immune system, such as an adhesion molecule or its ligand or surface receptors on a special class of cells. These targeted perturbations of the immune system increase the risk of particular infectious diseases. For instance, natalizumab, an α4β1 integrin inhibitor that is highly effective in multiple sclerosis, increases the risk of progressive multifocal leukoencephalopathy for reasons that still remain unclear. It is likely that other therapies that result in a disruption of a specific component of the immune system will be associated with other unique opportunistic infections. The risk of multiple simultaneous neurological infections in the immunosuppressed host must always be considered, particularly with a failure to respond to a therapeutic regimen. With respect to appropriate and effective therapy, diagnostic accuracy assumes primacy, but occasionally broad spectrum therapy is necessitated. For a number of opportunistic infectious disorders, particularly some viral and fungal diseases, antimicrobial therapy remains inadequate.

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Section: Treatmentmentioning

confidence: 99%

Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

Nath

Berger

2012

Curr Treat Options Neurol

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“…In 90-95% of cases, diffuse large B cell lymphoma (DLBCL) is diagnosed based on histopathological examination of the tumor. Much less common are T-cell lymphomas, Burkitt's lymphoma, lymphoblastic lymphomas and marginal zone lymphomas [2,3]. The pathogenesis of PCNSL remains unknown in most cases, but the defined risk factors for PCNSL include HIV infection or fully developed AIDS, inborn errors of immunity, and chronic immunosuppression after organ transplantation.…”

Section: Introductionmentioning

confidence: 99%

Treatment of primary central nervous system lymphoma (PCNSL) – single center experience.

Rybka,

Kuszczak,

Bogucka-Fedorczuk

2024

Acta Haematol Pol.

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“…Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) constitutes a rare disorder restricted to the cerebral parenchyma, leptomeninges, eyes or spinal cord observed with increasing incidence over recent decades, particularly in immunocompetent individuals [ 1 ]. With a median survival of three months in untreated individuals, prognosis of PCNSL is poor [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma

Wendler¹,

Fox

Valk³

et al. 2022

BMC Cancer

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Background Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT. Methods This is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months. Discussion Current treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy. Trial registration German clinical trials registry DRKS00022768 registered June 10th, 2021.

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Treatment approaches for primary CNS lymphomas

Cited by 16 publications

References 76 publications

Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

Treatment of primary central nervous system lymphoma (PCNSL) – single center experience.

Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma

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