Application of new targeted drugs in relapsed/refractory primary central nervous system lymphoma

Zhou, Ying; Xu, Xiaohong

doi:10.1080/16078454.2021.2019363

Cited by 4 publications

(4 citation statements)

References 37 publications

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“… 18 , 26 , 37 – 39 Lenalidomide and the Bruton tyrosine kinase inhibitors have limited activity as monotherapies for CNS involvement by aggressive B-cell lymphoma but are being evaluated in combination with chemotherapy and novel agents. 40 – 42 Despite the recent approvals of several new agents in relapsed/refractory DLBCL and HGBL, treatment of CNS involvement remains an unmet need as these agents have largely not been tested in patients with CNS involvement and likely have limited efficacy in this setting. 43 – 46 One important exception might be CAR T cells with emerging data showing feasibility and efficacy, although the majority of patients still need effective bridging therapies.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Fleming

Huang

Dotson

et al. 2022

Therapeutic Advances in Hematology

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Background: The optimal treatment of patients with systemic diffuse large B-cell (DLBCL) or high-grade B-cell (HGBL) lymphomas with synchronous central nervous system (CNS) involvement at diagnosis is not well defined. High-dose methotrexate administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited. Objective: To report our experience with RM-CHOP in patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis. Design: A single-center retrospective analysis. Methods: We identified consecutive patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis who were treated with RM-CHOP from January 2012 to January 2021. Results: Fifty patients were included with a median age of 62 years; 82% had DLBCL ( n = 41) and 18% had HGBL ( n = 9). Treatment with RM-CHOP was followed by consolidative autologous hematopoietic cell transplantation in 14 patients (28%). The complete response (CR) rate following RM-CHOP was 62%. With a median follow-up of 40 months, the median progression-free (PFS) and overall (OS) survivals were 16 and 58 months, and the 2-year PFS and OS were 41% and 57%, respectively. The 2-year cumulative incidence of CNS progression/relapse was 29%. Outcomes were particularly poor in HGBL, with median PFS and OS of 6 and 7 months, compared with median PFS and OS of 22 months and not reached in DLBCL, respectively. The outcomes of patients with relapsed/progressive disease were poor, with only 63% of patients receiving subsequent treatments and only 21% achieving CR to next subsequent treatment. Most patients (58%) with disease relapse/progression had CNS involvement which was associated with very poor outcomes (median OS of 2 months). Conclusion: CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis dictates clinical outcomes and requires more effective treatment options.

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Section: Discussionmentioning

confidence: 99%

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Fleming

Huang

Dotson

et al. 2022

Therapeutic Advances in Hematology

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“…It has become a research hotspot in recent years to apply new targeted drugs to improve the prognosis of patients with recurrent refractory type CNS lymphoma by studying gene mutations and signal transduction pathways to find new therapeutic targets, such as Bruton tyrosine kinase, mammalian target of rapamycin, immune checkpoint, and phosphatidylinositol 3-kinase inhibitors, and immunomodulators, have been used in the treatment of recurrent, refractory primary CNS diffuse large B-cell lymphoma. [17] In summary, when the patient's complete nervous system examination, head trauma history, and head CT imaging characteristics are inconsistent, if conditions permit, further imaging examination can be carried out to help diagnose. Emergency surgery is a choice when the patient's condition does not allow it.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Subdural anaplastic large-cell lymphoma presenting as a subacute epidural hematoma on imaging: A case report

Yin²,

Huo

et al. 2022

Medicine

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Rationale: Subdural anaplastic large-cell lymphoma (SALCL) is an extremely rare subtype of primary central nervous system (CNS) lymphoma. Here, we report a very rare subdural lymphoma case, which was misdiagnosed as a subacute epidural hematoma based on the radiological examination.Patient concerns: We present the case of an 82-year-old patient who presented with a 2-day history of headache and consciousness disorder following head injury. Computed tomography of the head revealed a fusiform isodense/slightly dense shadow under the right temporoparietal occipital cranial plate, suggesting a subacute epidural hematoma. It was initially misdiagnosed as a right traumatic subacute epidural hematoma with hemiplegia of the left limb. According to the patient's condition, an emergency craniotomy was performed to remove the hematoma. However, it was found that the lesion was located under the dura mater and was yellowish-brown with yellowish-brown liquid inside. The appearance of the lesion looked like bean curd residue. Histopathological examination diagnosed ALCL.Diagnosis: SALCL presenting as a subacute epidural hematoma on imaging.Interventions: Operation.Outcomes: The patient died 1 month after being discharged automatically.Conclusions: This report shows a rare radiography presentation of SALCL. SALCL can mimic the appearance of an epidural hematoma and should be regarded as a differential diagnosis even in patients with a history of craniocerebral injury and the "typical" imaging appearance of an epidural hematoma. The report is hoped to provide a scientific reference for the clinical diagnosis of subdural lymphoma.

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“…Other frequent alterations in PCNSL, such as MYD88 and CD79B mutations present in 50-80% of PCNSL [96,102,103], were not prognostic, and would not accurately predict its response to ibrutinib in contrast to what systemic DLBCL had shown [104]. Some gene alteration profiles such as coexpression of BCL2-MYC [105] and CD79B and/or PIM1 mutations have been correlated with poor OS [106].…”

Section: Molecular Genetic Markersmentioning

confidence: 97%

Prognostic factors in primary central nervous system lymphoma

Morales-Martínez¹,

Nichelli

Hernández-Verdin

et al. 2022

Current Opinion in Oncology

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Purpose of reviewPrimary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal diffuse large B cell lymphoma. Despite its apparent immunopathological homogeneity, PCNSL displays a wide variability in outcome. Identifying prognostic factors is of importance for patient stratification and clinical decision-making. The purpose of this review is to focus on the clinical, neuroradiological and biological variables correlated with the prognosis at the time of diagnosis in immunocompetent patients.Recent findingsAge and performance status remain the most consistent clinical prognostic factors. The current literature suggests that neurocognitive dysfunction is an independent predictor of poor outcome. Cumulating data support the prognostic value of increased interleukin-10 level in the cerebrospinal fluid (CSF), in addition to its interest as a diagnostic biomarker. Advances in neuroimaging and in omics have identified several semi-quantitative radiological features (apparent diffusion restriction measures, dynamic contrast-enhanced perfusion MRI (pMRI) pattern and 18F-fluorodeoxyglucose metabolism) and molecular genetic alterations with prognostic impact in PCNSL.SummaryValidation of new biologic and neuroimaging markers in prospective studies is required before integrating future prognostic scoring systems. In the era of radiomic, large clinicoradiological and molecular databases are needed to develop multimodal artificial intelligence algorithms for the prediction of accurate outcome.

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Application of new targeted drugs in relapsed/refractory primary central nervous system lymphoma

Cited by 4 publications

References 37 publications

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Subdural anaplastic large-cell lymphoma presenting as a subacute epidural hematoma on imaging: A case report

Prognostic factors in primary central nervous system lymphoma

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