scholarly journals Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review

2022 ◽  
Vol 14 (1) ◽  
pp. 99-108
Author(s):  
Gaurav Nepal ◽  
Mahika Khurana ◽  
Domenica Herrera Bucheli ◽  
Siddhartha Bhandari ◽  
Utsav Joshi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Central Nervous System ◽  
Nervous System ◽  
Significant Proportion ◽  
Central Nervous System Lymphoma ◽  
The Novel ◽  
Non Hodgkin Lymphoma ◽  
Frequent Relapses ◽  
Btk Inhibitor ◽  
The Brain

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1–2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.

Nonglial Central Nervous System Tumors

2021 ◽  
pp. 931-948
Author(s):  
Akanksha Sharma ◽  
Alyx B. Porter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Highly Active Antiretroviral Therapy ◽  
Central Nervous System Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Highly Active ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Adjusted Incidence ◽  
The Brain

Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that may involve the brain, leptomeninges, eyes, or spinal cord and accounts for up to 5% of all adult primary brain neoplasms. Age-adjusted incidence has increased in the past 3 decades. Infection with HIV and acquired immunodeficiency syndrome increase the risk of PCNSL by 3,600-fold. However, with highly active antiretroviral therapy, the frequency of immune system compromise sufficient for HIV-associated PCNSL (CD4 count ≤50) is dramatically reduced, along with the risk of this disorder.

Discovery of HBW-3-20, the first potent reversible inhibitor of Bruton’s tyrosine kinase (BTK) with high brain exposure.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15068-e15068
Author(s):  
Ning Lee ◽  
Yingfu Li ◽  
Chester Yuan ◽  
Guanfeng Liu ◽  
Chunchao Yue
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Central Nervous System Lymphoma ◽  
Autoimmune Disorders ◽  
Wild Type ◽  
High Brain ◽  
Brain Exposure ◽  
Btk Inhibitor ◽  
The Brain

e15068 Background: It has been an on-demand task to develop a BTK inhibitor of significant brain exposure, a critical property for extending its usages to treat Primary Central Nervous System Lymphoma (PCNSL) and autoimmune disorders. PCNSL is an aggressive extra nodal non-Hodgkin lymphoma that exclusively invades the central nervous system (CNS). Tirabrutinib, an irreversible BTK inhibitor with limited brain exposure, is the first BTK inhibitor approved for the treatment of recurrent or refractory primary central nervous system lymphoma recently. PRN2246 is another irreversible BTK inhibitor claimed to be of brain exposure, and is currently in clinical trials for the treatment of multiple sclerosis. Methods: New reversible BTK inhibitors were designed, synthesized and tested for enzymatic activities against wild-type and C481S-mutated BTK. Highly active compounds were confirmed for growth effects in diffuse large B-cell lymphoma derived TMD8 cells. Their microsomal stability and ADME properties were also assessed. Potent and bioavailable compounds were further measured for brain exposures in rats. Results: HBW-3-20 has excellent potency against both wild-type and C481S-mutated BTK, with IC50 of 2.5 and 3.8 nM, respectively. Its TMD8 cellular potency is 72 nM. In a head-to-head direct comparison of brain exposure experiment, HBW-3-20, tirabrutinib and PRN2246 were all dosed at 10mg/kg orally. The brain and plasma concentration were measured after 1 hour and the data are shown in the table below. The brain to plasma ratio for HBW-3-20, tirabrutinib and PRN2246 are 58%, 11.8% and 4.2% respectively. Our results show that HBW-3-20 has much greater brain permeability than tirabrutinib or PRN2246 in rats. Conclusions: HBW-3-20 is the first potent reversible BTK inhibitor that shows promisingly high brain permeability. HBW-3-20 provides a very valuable clinical candidate for treating B-cell malignancies in brain and autoimmune disorders![Table: see text]

scholarly journals Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1076
Author(s):  
Marietya I. S. Lauw ◽  
Calixto-Hope G. Lucas ◽  
Robert S. Ohgami ◽  
Kwun Wah Wen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Genetic ◽  
Central Nervous System Lymphoma ◽  
Great Majority ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Genetic Features ◽  
The Central Nervous System ◽  
The Brain

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90–95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed.

scholarly journals Primary central nervous system lymphoma

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 379-385 ◽  
Author(s):  
Tracy T. Batchelor
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Hodgkin Lymphoma ◽  
Central Nervous System Lymphoma ◽  
The Body ◽  
Immunocompetent Host ◽  
Non Hodgkin Lymphoma ◽  
Organ Specific ◽  
The Brain

Abstract 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.

scholarly journals RARE-29. PRIMARY CENTRAL NERVOUS SYSTEM NON-HODGKIN LYMPHOMA IN AN 11-YEAR-OLD BOY: A CASE REPORT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii448-iii448
Author(s):  
Jorge Luis Ramírez-Melo ◽  
Regina M Navarro-Martin del Campo ◽  
Manuel D Martinez-Albarran ◽  
Fernando Sánchez-Zubieta ◽  
Ana L Orozco-Alvarado ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hodgkin Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Complete Response ◽  
High Dose ◽  
Illustrative Case ◽  
Tumor Biopsy ◽  
Non Hodgkin Lymphoma ◽  
The Right

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) are very rare in children. CLINICAL CASE: An 11-year-old male presented with a 2 months history with myoclonic movements in the upper right limb, and a sudden frontal headache, gait disturbance due to right hemiparesis and an ipsilateral convulsive episode. Upon admission he had critical condition, with hypertensive skull syndrome, Glasgow of 12, Karnofsky 40%, right hemiparesis, swallowing disorder, facial paralysis, and loss of photo motor reflex and unilateral amaurosis. A CT and MRI showed a huge tumor mass in the left tempo-parietal region, infiltrating the white matter and shifting the midline. A Tumor biopsy was done, and reported diffuse small cell non-Hodgkin lymphoma of high-grade, Burkitt type. Systemic lymphoma workup was negative. He received six cycles of chemotherapy based on high dose methotrexate, rituximab and triple intrathecal.After the second cycle an ophthalmologic evaluation was done, and found infiltration to the right retina, for which 6 cycles of intra vitreous chemotherapy with methotrexate were applied, he showed an excellent response, and recovered all his neurological functions except that right hemianopia persist. Control MRI showed partial response at 2nd cycle and complete response after the 4th cycle. No Radiation was performed. CONCLUSION This report highlights the fact that pediatric PCNSL may be effectively treated by a combination of HDMTX and rituximab-based chemoimmunotherapy without irradiation. Lack of awareness of this rare entity may lead to extense resections of brain, and potential permanent secuelae that were avoided in this illustrative case.

Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 466-468 ◽  
Author(s):  
James L. Rubenstein ◽  
Dan Combs ◽  
Jay Rosenberg ◽  
Arthur Levy ◽  
Michael McDermott ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hodgkin Lymphoma ◽  
Phase 1 ◽  
Central Nervous System Lymphoma ◽  
Serum Levels ◽  
Pharmacokinetic Analysis ◽  
Lymphomatous Meningitis ◽  
Cell Surface Molecule ◽  
Non Hodgkin Lymphoma

Most lymphomas that involve the central nervous system are B-cell neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in the cerebrospinal fluid (CSF) in patients with primary central nervous system lymphoma; however, the CSF levels of rituximab are approximately 0.1% of serum levels associated with therapeutic activity in patients with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is a frequent complication of non-Hodgkin lymphoma, we have conducted an analysis of the safety and pharmacokinetics of direct intrathecal administration of rituximab using cynomolgus monkeys. No significant acute or delayed toxicity, neurologic or otherwise, was detected. Pharmacokinetic analysis suggests that drug clearance from the CSF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent lymphomatous meningitis will be implemented based on these findings.

Unilateral Seizures following Vincristine Intravenous Injection

1984 ◽  
Vol 70 (3) ◽  
pp. 243-244 ◽  
Author(s):  
Francesco Dallera ◽  
Roberto Gamoletti ◽  
Paolo Costa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Intravenous Injection ◽  
Central Nervous System Toxicity ◽  
Computed Tomographic ◽  
Non Hodgkin Lymphoma ◽  
The Face ◽  
Lymphomatous Involvement ◽  
The Brain ◽  
System Toxicity

A case of acute central nervous system toxicity following the intravenous injection of vincristine was observed in a patient treated with a chemotherapy regimen including cyclophosphamide, doxorubicin and prednisone for non-Hodgkin lymphoma. The neurological symptoms consisted of right-sided epileptiform jacksonian seizures limited to the face, that lasted about 10 min, followed by spontaneous recovery. A cerebrospinal fluid study and computed tomographic scan of the brain failed to reveal any central nervous system lymphomatous involvement.

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