Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

Cheah, Chan Yoon; George, Anupkumar; Giné, Eva; Chiappella, Annalisa; Kluin-Nelemans, Hanneke C.; Jurczak, Wojciech; Krawczyk, Katarzyna; Móciková, Heidi; Klener, Pavel; Schwartz, David A.; Walewski, Jan; Szymczyk, Michał; Smolej, Lukáš; Auer, Rebecca; Ritchie, David; Arcaini, Luca; Williams, Michael E.; Dreyling, Martin; Seymour, John F.

doi:10.1093/annonc/mdt139

Cited by 117 publications

(116 citation statements)

References 22 publications

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“…The highly active therapeutic activity for these patients after single oral agent ibrutinib therapy, with clinical and objective responses within 3 months, seems to be very promising. Survival after CNS relapse diagnosis for these patients is already substantially higher than the median 3.7 months reported, 2 and for two of them, follow-up at 1 year and at 9 months showed a persisting CR, confirming the efficacy of ibrutinib.…”

Section: Resultssupporting

confidence: 53%

“…Although infrequent, it has rapidly fatal consequences with a poor median survival. 2 CNS relapse in MCL is a significant unmet medical need and its very poor prognosis with current treatment options 11 highlights the urgent need for alternative therapeutic approaches. This is the first report describing the efficacy of ibrutinib in MCL patients with CNS relapse.…”

Section: Resultsmentioning

confidence: 99%

“…1 Central nervous system (CNS) dissemination occurs in 4.1% of these patients during the course of the disease. 2 Median survival after diagnosis of CNS involvement is 3.7 months. 2 Ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, acts by blocking B-cell antigen receptor signaling, thereby reducing malignant proliferation of B cells and inducing apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…2 Median survival after diagnosis of CNS involvement is 3.7 months. 2 Ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, acts by blocking B-cell antigen receptor signaling, thereby reducing malignant proliferation of B cells and inducing apoptosis. 3 Ibrutinib is a highly active novel agent with durable single-agent activity in relapsed and refractory MCL, giving a 68% response rate in a cohort of patients with relapsed/refractory MCL.…”

Section: Introductionmentioning

confidence: 99%

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Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse

Bernard

Goldwirt

Amorim

et al. 2015

Blood

132

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Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse

Bernard

Goldwirt

Amorim

et al. 2015

Blood

132

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“…11,13,14 Older age, involvement of the central nervous system or bone marrow, and relapse after bone marrow transplantation have been implicated with a worse lymphoma prognosis. 18,19,20 Although their continued relevance in the rituximab/Positron Emission Tomography era has been called into question, 18 the Ann Arbor stage 21 and Age-adjusted International Prognostic Index 22 are tools used to determine lymphoma prognosis. These studies also include age, stage, serum lactate dehydrogenase (LDH) and performance status in their models.…”

Section: Discussionmentioning

confidence: 99%

Frequency and Reasons for Return to the Primary Acute Care Service among Lymphoma Patients Undergoing Inpatient Rehabilitation

Fu¹,

Lee²,

Smith³

et al. 2013

PM&R

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Objective-To assess the frequency and risk factors for return to the primary acute care service among lymphoma patients undergoing inpatient rehabilitation.Design-Retrospective study. Setting-Tertiary referral-based cancer center.Patients-All patients with a history of lymphoma admitted to inpatient rehabilitation between October 1, 2003 and January 30, 2013.Main Outcome Measures-Items analyzed from patient records included return to the primary acute care service with demographic information, lymphoma characteristics, medications, hospital admission characteristics, and laboratory values.Results-143 unique patient admissions were analyzed. 54/143 (38%) of lymphoma inpatient rehabilitation admissions returned to the primary acute care service. However, 16/54 (30%) returned due to needing additional chemotherapy. Excluding patients who returned to the primary acute care service for chemotherapy, statistically significant or approaching statistically significant factors (p<.10) associated with return to the primary acute care service included a creatinine greater than or equal to 1.3 milligrams/deciliter (mg/dL) (p=0.0002), male sex (p=0.001), history Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosures: NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of hematopoietic stem cell transplant (p=0.0355), and presence of intravenous antifungal agent (p=0.0717). Of those transferred back to the primary acute care service; 13/38 (34%) discharged directly home, 10/38 (26%) died in the hospital, 7/38 (18%) transferred to a subacute rehabilitation facility, and 4/38 (11%) transferred to inpatient rehabilitation.Conclusions-Chemotherapy was the most common reason for return to the primary acute care service. When excluding patients who returned for chemotherapy, lymphoma patients who are male, who have had a hematopoietic stem cell transplant, and have a creatinine greater than or equal to 1.3 mg/dL demonstrated increased risk for return to the primary acute care service.

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Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.

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Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

Abstract: In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

Cited by 117 publications

References 22 publications

Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse

Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse

Frequency and Reasons for Return to the Primary Acute Care Service among Lymphoma Patients Undergoing Inpatient Rehabilitation

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

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