Treatment of Older Patients with Mantle-Cell Lymphoma

Kluin-Nelemans, Hanneke C.; Hoster, Eva; Hermine, Olivier; Walewski, Jan; Trněný, Marek; Geisler, Christian H.; Stilgenbauer, Stephan; Thiéblemont, Catherine; Vehling-Kaiser, Ursula; Doorduijn, Jeanette K.; Coiffier, Bertrand; Forstpointner, Roswitha; Tilly, Hervé; Kanz, Lothar; Feugier, Pierre; Szymczyk, Michał; Hallek, Michael; Kremers, Stephan; Lepeu, G.; Sanhès, Laurence; Zijlstra, Josée M.; Bouabdallah, Réda; Lugtenburg, Pieternella J.; Macro, Margaret; Pfreundschuh, Michael; Procházka, Vít; Raimondo, Francesco Di; Ribrag, Vincent; Uppenkamp, Michael; André, Marc; Klapper, Wolfram; Hiddemann, Wolfgang; Unterhalt, Michael; Dreyling, Martin

doi:10.1056/nejmoa1200920

Cited by 463 publications

(355 citation statements)

References 23 publications

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“…MCL is considered incurable; relapses are common, and MCL has a shorter overall survival (OS) compared with other lymphoma entities. In the past 20 years, the introduction of immunochemotherapy, 1,2 high-dose cytarabine (HA), 3,4 high-dose consolidation followed by autologous stem cell transplantation (ASCT), 5,6 bendamustine, 7 and rituximab maintenance 8 have substantially improved the outcome of patients with MCL. Currently, new targeted drugs that aim at long-term control or even cure of MCL are under investigation.…”

Section: Introductionmentioning

confidence: 99%

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures. Several studies have shown that intensification of initial treatment, which has resulted in improved clinical outcome, is immediately reflected in higher molecular remission rates; they have also shown that high-dose consolidation might not be able to compensate for less intensive induction regimens. Persistence or reappearance of MRD in clinical remission proved to be highly predictive for imminent clinical relapse associated with shorter overall survival. Therefore, the investigation of novel MRD-guided treatment strategies aimed at early eradication of MRD and pre-emptive treatment of molecular relapse seems warranted. Furthermore, the integration of MRD assessment into clinical response criteria could result in a more specific and potentially earlier end point for treatment efficacy. New technical developments such as high-throughput sequencing will further enhance the wide applicability of MRD detection in MCL.Learning Objectives

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Section: Introductionmentioning

confidence: 99%

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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“…Single agent fludarabine demonstrated an ORR < 40%; however, when combined with cyclophosphamide and rituximab the response rate is closer to 60% [31]. More recently, a large randomized trial done in Germany demonstrated that R-CHOP was superior to R-FC in the older MCL patient population with a 4 year OS of 65% for R-CHOP and 50% for R-FC (P 5 0.0032) [32]. In addition, a second randomization was done for maintenance either with rituximab or interferon.…”

Section: Initial Management Of Asymptomatic Low Mipi or Elderly MCL Pmentioning

confidence: 97%

Mantle cell lymphoma: 2015 update on diagnosis, risk‐stratification, and clinical management

Vose

2015

American J Hematol

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Disease Overview: Mantle cell lymphoma (MCL) is a non‐Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4‐5 years.Diagnosis: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX‐11 or a low Ki‐67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma.Risk Stratification: The MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki‐67 proliferative index if available. The median OS for the low‐risk group was not reached (5‐year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group.Risk‐Adapted Therapy: For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxic regimen ± autologous stem cell transplantation should be considered. For older MCL patients with intermediate or high risk MIPI, combination chemotherapy with R‐CHOP, R‐Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression‐free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti‐angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase [BTK] inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients. Am. J. Hematol. 90:740–745, 2015. © 2015 Wiley Periodicals, Inc.

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“…[15] Maintenance therapy with rituximab after induction with R-CHOP significantly improved OS (4-year survival rate, 87%, vs. 63% with interferon alfa; p = 0.005). [16] Intensive regimens, as sequential high-dose immune-chemotherapy including high-dose Ara-C followed by in vivo purged stem cell autograft, resulted in an OS of 89% and in an event-free survival of 79% at 54 months. [17] However, this approach is feasible in only a limited number of young patients.…”

Section: Chronic Lymphocytic Leukemiamentioning

confidence: 99%

Ibrutinib: another weapon in our arsenal against lympho-proliferative disorders

Cabras¹,

Angelucci²

2015

Expert Opinion on Pharmacotherapy

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In Volume 16, issue 12 of Expert Opinion on Pharmacotherapy, an important article on the new drug ibrutinib was published. This new drug promises to further improve outcome in the treatment of several lympho-proliferative disorders. In this editorial, the most important findings of the article looking particularly to the integration of ibrutinib in current clinical practice will be summarized. Finally this editorial will focus on the next challenges for scientists and physicians in the treatment of lympho-proliferative disorders.

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Treatment of Older Patients with Mantle-Cell Lymphoma

Cited by 463 publications

References 23 publications

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Mantle cell lymphoma: 2015 update on diagnosis, risk‐stratification, and clinical management

Ibrutinib: another weapon in our arsenal against lympho-proliferative disorders

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