Venetoclax penetrates in cerebrospinal fluid and may be effective in chronic lymphocytic leukemia with central nervous system involvement

Reda, Gianluigi; Cassin, Ramona; Dovrtělová, Gabriela Přibyl; Matteo, Cristina; Giannotta, Juri Alessandro; D'Incalci, M.; Cortelezzi, Agostino; Zucchetti, Massimo

doi:10.3324/haematol.2018.213157

Cited by 47 publications

(40 citation statements)

References 9 publications

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“…Venetoclax was also shown to be safe and effective in patients with previously treated WM (Castillo et al , ). A recent report demonstrated CNS penetration of venetoclax in a patient with relapsed CLL (Reda et al , ). The patient was treated with venetoclax and intrathecal chemotherapy, obtaining clinical improvement within one month of therapy.…”

Section: What Is Exciting On the Future Treatment Of Patients With Bns?mentioning

confidence: 98%

How we manage Bing–Neel syndrome

Castillo

Treon

2019

Br J Haematol

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Summary Bing–Neel syndrome (BNS) is an uncommon presentation of Waldenström macroglobulinaemia (WM), seen during the course of the disease in about 1% of patients. BNS occurs when WM cells gain access to the central nervous system (CNS) causing neurological deficits. The diagnosis of BNS is suggested by the presence of radiological abnormalities, such as leptomeningeal enhancement on magnetic resonance imaging and confirmed by the presence of clonal lymphoplasmacytic cells and MYD88 L265P in the cerebrospinal fluid. The treatment of BNS requires agents with good penetration into the CNS, such as fludarabine, methotrexate and cytarabine. The novel Bruton Tyrosine Kinase inhibitor ibrutinib has shown CNS‐penetrating properties, and recent data suggest a therapeutic role in BNS. In this review, we will discuss the clinical and pathological features, diagnostic criteria, treatment options and outcomes of patients with BNS.

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Section: What Is Exciting On the Future Treatment Of Patients With Bns?mentioning

confidence: 98%

How we manage Bing–Neel syndrome

Castillo

Treon

2019

Br J Haematol

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“…69 It has also been demonstrated to cross the BBB in CLL and is therefore of potential efficacy in CNS-MM. 70 Several phase III trials are currently underway using venetoclax in patients with RRMM.…”

Section: Future Directionmentioning

confidence: 99%

Multiple myeloma with central nervous system relapse

et al. 2020

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C entral nervous system involvement in multiple myeloma is a rare complication but carries a very poor prognosis. We provide a review of current literature, including presentation, treatment and survival data, and describe our experience in a regional hematologic malignancy diagnosis center where, over a 15-year period, ten cases were identified. Although the median age of onset, frequently between 50-60 years, is comparatively young, those diagnosed usually have a preceding diagnosis of multiple myeloma and often have had several lines of treatment. We discuss putative underlying factors such as prior treatment and associations including possible risk factors and features suggestive of a distinct biology. Central nervous system involvement may be challenging to diagnose in myeloma, displaying heterogeneous symptoms that can be confounded by neurological symptoms caused by the typical features of myeloma or treatment side-effects. We discuss the clinical features, imaging and laboratory methods used in diagnosis, and highlight the importance of considering this rare complication when neurological symptoms occur at presentation or, more commonly, during the disease pathway. In the absence of clinical trial data to inform an evidence-based approach to treatment, we discuss current and novel treatment options. Finally, we propose the establishment of an International Registry of such cases as the best way to collect and subsequently disseminate presentation, diagnostic and treatment outcome data on this rare complication of multiple myeloma.

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“…5,6 Venetoclax is a small molecule which is also able to cross the blood-brain barrier as reported in a recent case study demonstrating its clinical and radiological efficacy in a patient with CNS involvement. 7…”

Section: Introductionmentioning

confidence: 94%

“…The management of systemic relapse after ibrutinib treatment was completed with rituximab and venetoclax as described by Seymour et al 11 There is evidence supporting the use of rituximab to treat CNS involvement of B-cell malignancies such as primary CNS lymphoma. 12 But, the potency of venetoclax in treating CNS involvement as described by Reda et al 7 was not known at the beginning of our patient's treatment. As a matter of fact, the need to quickly control neurological symptoms was another argument in favor of the administration of high-dose methotrexate in our case.…”

Section: Case Presentationmentioning

confidence: 99%

“…Venetoclax, an oral BCL‐2 inhibitor, has recently proven to be effective for refractory/relapsed CLL when administered with or without rituximab . Venetoclax is a small molecule which is also able to cross the blood‐brain barrier as reported in a recent case study demonstrating its clinical and radiological efficacy in a patient with CNS involvement …”

Section: Introductionmentioning

confidence: 99%

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