Advances in chronic lymphocytic leukemia pharmacotherapy

Gomes, Lorena Caixeta; Ferrão, Aline Lúcia Menezes; Evangelista, Fernanda Cristina Gontijo; Almeida, Tâmara Dauare de; Barbosa, Rayson Carvalho; Carvalho, Maria das Graças; Sabino, Adriano de Paula

doi:10.1016/j.biopha.2017.10.105

Cited by 15 publications

(11 citation statements)

References 79 publications

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“…B-ćelijski receptor je transmembranski receptorski kompleks povezan sa B-ćelijskom signalnom transdukcijom i kao takav je ključan za normalnu maturaciju B-ćelija (16). Signalna transdukcija BCR ima značajan uticaj i na rast i razvitak malignih klonova B-ćelija (17). Značaj proteina povezanih sa BCR pokazan je u brojnim kliničkim studijama u kojima su korišćeni molekuli inhibitori različitih kinaza povezanih sa BCR (18).…”

Section: Prognostički Faktori I Novi Terapijski Agensi U Lečenju Hronunclassified

“…Ovaj protein je eksprimiran u hematopoeznim ćelijama, posebno B-limfocitima, ali nije eksprimiran na T-i plazmatskim ćelijama (19,20). Aktivacija BTK rezultira aktivacijom transkripcionih faktora neophodnih za proliferaciju i diferencijaciju B-ćelija (17). Dodatno, BTK je bitan za motilitet i "tissue homing" B-ćelija, reguliše odgovor na hemokine i integrine sekretovane od strane ćelijske mikrosredine, što naposletku objašnjava kretanje limfocita između limfnih čvorova i krvi, kao i posledičnu početnu leukocitozu koja se viđa u bolesnika lečenih inhibitorima BTK (slika 1) (19).…”

Section: Inhibitori Brutonove Tirozin Kinazeunclassified

“…Molekul CD19 je izabran kao idealni ciljni molekul jer je eksprimiran samo na B-ćelijama, a ne eksprimiraju ga hematopoezne stem ćelije niti ćelije drugih tkiva (47). Himerični antigenski receptor T-ćelija (CAR T) kombinuje ciljnu specifičnost monoklonskog antitela sa intraćelijskom aktivacijom T-ćelijskog signalnog puta; drugim rečima, CAR T usmerava autolognu ćelijsku citotoksičnost prema malignim ćelijama koje eksprimiraju ciljni antigen (17). Hronična limfocitna leukemija predstavlja jednu od bolesti u čijem je lečenju prvi put upotrebljena CAR T, ali je danas objektivno primat na lečenju B-akutne limfoblastne leukemije (B-ALL) i agresivnih nehočkinskih (engl.…”

Section: Terapija Himeričnim Antigenskim Receptorom T-ćelija (Engl Cunclassified

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Prognosis and new therapeutic approaches in chronic lymphocytic leukemia treatment

Otašević¹,

Mihaljević²

2019

Medicinski podmladak

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Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, comprising about 30% of all leukemias in Europe and United States. Also, it represents one of the most active hematological disease regarding clinical trials. Nearly 80% of CLL patients have some chromosomal aberration, with following being emphasized due to its frequency and importance: 13q14 deletion (del13q14), 11q22-q23 deletion (del11q), chromosome 12 trisomy, 17p deletion (del17p) or/and tumor suppressor gene TP53 mutation. The use of new therapeutic agents in CLL treatment has markedly improved survival and quality of life of CLL patients. Ibrutinib, Bruton's kinase inhibitor (BTK), is approved for first line therapy for CLL patients with del17p or TP53 mutation, as well for relapsed/refractory CLL patients (R/R CLL). The use of venetoclax, antiapoptotic protein bcl-2 inhibitor, is indicated for R/R CLL patients who are resistant to ibrutinib or for whose ibrutinib is contraindicated (use of anticoagulant therapy; increased bleeding risk). Phosphoinositide 3-kinase (PI3K), idelalisib (in combination with rituximab) and duvelisib (monotherapy), are approved for treatment of R/R CLL patients. The PI3K inhibitors are rarely used in treatment of R/R CLL patients before ibrutinib or venetoclax, primarily because of unfavourable safety profile of these drugs. New therapeutic agents are providing CLL patients longer overall survival and progression free survival, especially for CLL patients with adverse prognostic factors.

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Section: Prognostički Faktori I Novi Terapijski Agensi U Lečenju Hronunclassified

Section: Inhibitori Brutonove Tirozin Kinazeunclassified

Section: Terapija Himeričnim Antigenskim Receptorom T-ćelija (Engl Cunclassified

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Prognosis and new therapeutic approaches in chronic lymphocytic leukemia treatment

Otašević¹,

Mihaljević²

2019

Medicinski podmladak

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“…In India, incidence rates of 2.9 and 1.5 per 100,000 have been reported in men and women, respectively [1][2][3]. Chronic lymphocytic leukemia (CLL) often grouped as NHL, is a lymphoproliferative disease that has a highly variable clinical course and may involve the bone marrow, blood, and solid lymphoid organs [4].…”

Section: Introductionmentioning

confidence: 99%

“…However, in many patients, the presence of comorbidities, low bone marrow reserve, acquired genetic mutations make the treatment suboptimal and resulting in relapse [6]. During the recent years, research has focused on drugs targeting novel mechanisms such as Bruton's tyrosine kinase and apoptosis proteins [4].…”

Section: Introductionmentioning

confidence: 99%

Ibrutinib in the Management of Non-Hodgkin’s Lymphoma: A Case Report

Pavithran

2018

Asian J Pharm Clin Res

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Non-Hodgkin's lymphoma (NHL) is a diverse group of lymphoid neoplasms, the prevalence of which has increased over the past few decades. NHL is diverse in the manner of presentation, response to various treatment and prognosis. The current case report describes a 40-year-old man who was diagnosed with small lymphocytic lymphoma/chronic lymphocytic leukemia in 2006. The patient had disease progression during the course of 10 years from the time of diagnosis for which he received multiple lines of chemotherapy (chlorambucil/prednisolone; rituximab/cyclophosphamide/ fludarabine; bendamustine/rituximab; and ofatumumab). However, in 2016, his disease again showed signs of progression, and hence he was started on ibrutinib 140 mg 3 times daily. After treatment with ibrutinib, there were no clinical nodes and hepatosplenomegaly, and all counts also normalized. Since the commencement of this agent, no disease progression was observed for almost 16 months. However, in July 2017, again disease progression occurred, and the patient was started on with cyclophosphamide, vincristine, and prednisone (COP) regimen. He received one cycle of COP regimen and continued on treatment with ibrutinib, and the treatment was well tolerated. In December 2017, he expired due to the progression of the disease. Ibrutinib, a Bruton's tyrosine kinase inhibitor, appears to be safe and effective in providing long-term disease control even in refractory cases of NHL.

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