Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma

Robak, Tadeusz; Huang, Huiqiang; Jin, Jie; Zhu, Jun; Liu, Ting; Samoilova, Olga; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Osmanov, Evgenii A.; Alexeeva, Julia; Pereira, Juliana; Drach, Johannes; Mayer, Jiřı́; Hong, Xin; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; Velde, Helgi van de; Cavalli, Franco

doi:10.1056/nejmoa1412096

Cited by 337 publications

(265 citation statements)

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“…158 In both examples, the ability of a specific agent (e.g., oxaliplatin, cyclophosphamide) but not one of its alike (e.g., cisplatin, melphalan) to drive ICD can be explained by the differential activation of ER stress (and hence differential exposure of CALR in the course of RCD). 100,[157][158][159] Well established ICD inducers include commonly employed anticancer chemotherapeutics such as: (1) (6) bortezomib, a proteasomal inhibitor approved for the therapy MM and mantle cell lymphoma (MCL); [171][172][173][174][175][176][177][178][179][180][181] (7) cyclophosphamide, a DNA-alkylating agent approved for use in patients with chronic myeloid leukemia (CML), AML, ALL, chronic lymphocytic leukemia, MM, ovarian carcinoma, breast carcinoma, mycosis fungoides, lymphoma, neuroblastoma, and retinoblastoma; 177,[182][183][184][185][186][187][188][189][190][191] and (8) oxaliplatin, a platinum-derivative licensed for the therapy of advanced colorectal carcinoma in combination with 5-fluorouracil and folinic acid. 156,157,[192][193][194][195][196][197][198] Moreover, there is some evidence that microtubule-targeting agents including taxanes and vinca alkaloids (which are commonly used for the treatment of multiple carcinomas) can stimulate ICD.…”

Section: Introductionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

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Section: Introductionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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“…vs. 24.7 mo. ; P < 0.001) the median OS was 56.3% vs. not reached (hazard ratio 0.80) [30]. This may be an option in patients who are not eligible for transplant and don't have pre-existing peripheral neuropathy.…”

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

confidence: 94%

“…Some clinical studies are testing agents used in relapsed MCL in combinations in the front-line setting such as R-CHOP 1 Bortezomib [30]. A large phase III trial of R-CHOP vs. bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) demonstrated a 59% improvement in PFS (median 14.4 mo.…”

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

confidence: 99%

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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“…Бортезомиб је 2014. год. одобрен за пацијенте који су већ примили иницијалну терапију 24,25,26 . Код млађих пацијената се може размотрити алогена трансплантација 27 .…”

Section: дискусијаunclassified

Primary mantle cell lymphoma of tonsil: Case report

Knežević¹

2017

Opsta med

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СажетакУвод. Mantle cell lymphoma је редак подтип B-ћелијског лимфома. Обухвата 4%-6% свих нехочкинских лимфома (NHL). Чешћи је код старијих мушкараца у односу на друге подтипове лимфома; средња старост оболелих је 65 година. Примарни тонзиларни лимфом чини мање од 1% малигнитета главе и врата.Циљ рада. Указати на значај ране и тачне дијагнозе и благовременог лечења малигних болести.Метод. Mantle cell лимфом. Мултислајсна компјутеризована томографија (MSCT) врата, грудног коша и горњег абдомена: лева тонзила је промера 28 mm x 32 mm, у дужини 36 mm, лобулараних контура, хетерогене структуре, асиметрично сужава попречни лумен дисајног стуба на 7 mm. Патолошки увећани лимфни нодуси промера 10 mm до 15 mm субмандибуларно и лево парајугуларно. У плућном паренхиму нема патолошких промена. Нема увећаних лимфних нодуса у абдомену и ретроперитонеалном простору. Абдоминални органи у физиолошким границама. Биопсија коштане сржи: нема знакова лимфопролиферативног обољења. Хемалошки конзилијум: NHL Mantle cell lymphoma CS IIAE. Хемотерапија по протоколу: циклофосфамид, доксорубицин, винкристин и преднизолон (CHOP), ординирано шест циклуса. Лева тонзила се после другог циклуса хемотерапије смањила а пацијенту је било олакшано дисање и узимање хране; терапију примио до краја, јавља се на редовне контроле. Kључне речи:примарна здравствена заштита, дијагноза, генетика, општа медицина, лимфом.

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Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma

Abstract: VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.).

Cited by 337 publications

References 34 publications

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

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

Primary mantle cell lymphoma of tonsil: Case report

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