Opinia ekspertów dotycząca stosowania akalabrutynibu w leczeniu przewlekłej białaczki limfocytowej DOI Open Access
Bartosz Puła, Elżbieta Iskierka‐Jażdżewska, Krzysztof Jamroziak

et al.

Published: Dec. 20, 2024

Inhibitory kinazy tyrozynowej Brutona stały się jednymi z najważniejszych leków w leczeniu pacjentów przewlekłą białaczką limfocytową (CLL). BTK są obecnie dobrze ugruntowaną terapią dla nieleczonych, jak również nawrotem lub opornych na leczenie. Wykazano, że BTKis kluczowe CLL wysokiego ryzyka aberracjami genu TP53 charakteryzujących niezmutowanym statusem regionu zmiennego łańcucha ciężkiego immunoglobulin ( IGHV ). Ibrutynib był pierwszym swojej klasie inhibitorem BTK; jednak pomimo jego potencjału terapeutycznego, charakteryzuje on określonymi działaniami niepożądanymi, tym nadciśnieniem tętniczym, zwiększonym ryzykiem krwawienia, toksycznością kardiologiczną i zmianami skórnymi. Chociaż wykazano, następna generacja jest bardziej specyficzna, ten profil zdarzeń niepożądanych uważany za specyficzny tej klasy leków. W niniejszym przeglądzie omówiono aktualny status akalabrutynibu, BTKi drugiej generacji.

A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia DOI Open Access
Kamil Wiśniewski, Bartosz Puła

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5246 - 5246

Published: May 11, 2024

Bruton's Tyrosine Kinase (BTK) inhibitors have become one of the most vital drugs in therapy chronic lymphocytic leukemia (CLL). Inactivation BTK disrupts B-cell antigen receptor (BCR) signaling pathway, which leads to inhibition proliferation and survival CLL cells. (BTKi) are established as leading treatment both treatment-naïve (TN) relapsed or refractory (R/R) CLL. Furthermore, BTKi demonstrate outstanding efficacy high-risk CLL, including patients with chromosome 17p deletion, TP53 mutations, unmutated status immunoglobulin heavy-chain variable region (IGHV) gene. Ibrutinib is first-in-class has changed landscape Over last few years, novel, covalent (acalabrutinib, zanubrutinib), non-covalent (pirtobrutinib) been approved for Unfortunately, continuous contributes acquisition secondary resistance clinical relapse. In recent it demonstrated that predominant mechanisms mutations phospholipase Cγ2 (PLCG2). Some differences identified despite their similar mechanism action. Moreover, novel resulting recently suggested. This article summarizes latest data regarding all registered BTKi.

Language: Английский

Citations

5
Extramedullary and extranodal manifestations in chronic lymphocytic leukemia – an update DOI Creative Commons
Tadeusz Robak, Anna Puła, Marcin Braun

et al.

Annals of Hematology, Journal Year: 2024, Volume and Issue: 103(9), P. 3369 - 3383

Published: July 25, 2024

Chronic lymphocytic leukemia/small lymphoma (CLL/SLL) is a common leukemia characterized by clonal expansion of mature CD5+/CD23 + B cells in the blood, bone marrow (BM) and lymphoid tissues. CLL can undergo extramedullary extranodal infiltration, with one study noting an incidence only 0.3 per 100,000 people, 17.6% patients another report. The most sites leukemic involvement are skin central nervous system; however, other organs, including liver, lungs, kidney, gastrointestinal tract, bone, prostate heart, occasionally involved. prognostic significance extra-medullary still under debate, but prognosis such seems to be better era novel targeted drugs. Following diagnosis CLL, survival appears depend on site infiltration. This review presents overview lesions, focusing its epidemiology, pathogenesis, prognosis, clinical characteristics treatment results.

Language: Английский

Citations

5
PI3K/AKT confers intrinsic and acquired resistance to pirtobrutinib in chronic lymphocytic leukemia DOI Creative Commons
Chunfang Kong, Mei Wu, Qilin Lu

et al.

Leukemia Research, Journal Year: 2024, Volume and Issue: 144, P. 107548 - 107548

Published: July 7, 2024

Pirtobrutinib, a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, has been approved as the first agent to overcome resistance covalent BTK inhibitors (such ibrutinib, acalabrutinib, and zanubrutinib). However, mechanisms of pirtobrutinib in chronic lymphocytic leukemia (CLL) remain poorly understood.

Language: Английский

Citations

2
Efficacy and Effectiveness Outcomes of Treatments for Double‐Exposed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Patients: A Systematic Literature Review DOI Creative Commons
Mohammed Zuber, Sreelatha Akkala, Niying Li

et al.

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(18)

Published: Sept. 1, 2024

Bruton's tyrosine kinase inhibitors (BTKi) and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax have significantly improved outcomes achieved durable remission in patients with chronic lymphocytic leukemia (CLL). BTKi/venetoclax-treated exposure to both novel agents (regardless of reason for discontinuation) are classified as "double-exposed," often poor prognoses. This study aims assess efficacy effectiveness treatments double-exposed CLL patients.

Language: Английский

Citations

1
BCL-2 and BTK inhibitors for chronic lymphocytic leukemia: current treatments and overcoming resistance DOI
Tadeusz Robak, Magdalena Witkowska, Anna Wolska

et al.

Expert Review of Hematology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

In the last decade, BTK inhibitors and BCL-2 inhibitor venetoclax have replaced immunochemotherapy in treatment of CLL.

Language: Английский

Citations

1
Metabolic and toxicological considerations of Bruton’s tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma DOI
Anna Wolska, Paweł Robak, Magdalena Witkowska

et al.

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2024, Volume and Issue: 20(4), P. 207 - 224

Published: March 22, 2024

Bruton tyrosine kinase inhibitors (BTKi) have been used for the management of human diseases since approval first-in class agent, ibrutinib, by Food and Drug Administration in 2013 treatment patients with mantle cell lymphoma (MCL). Ibrutinib is a covalent inhibitor along second-class BTKis: acalabrutinib zanubrutinib. These well-tolerated agents transformed landscape chronic lymphocytic leukemia/small (CLL/SLL). A new these inhibitors, non-covalent, might become an answer to emerging resistance avoiding sustained contact binding domain.

Language: Английский

Citations

0
Synthesis and Biochemical Evaluation of Ethanoanthracenes and Related Compounds: Antiproliferative and Pro-Apoptotic Effects in Chronic Lymphocytic Leukemia (CLL) DOI Creative Commons

James P. McKeown,

Andrew J. Byrne,

Sandra A. Bright

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(8), P. 1034 - 1034

Published: Aug. 5, 2024

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells, and it the most frequent form diagnosed in Western countries. It characterized by proliferation accumulation neoplastic lymphocytes blood, lymph nodes, bone marrow spleen. We report synthesis antiproliferative effects series novel ethanoanthracene compounds CLL cell lines. Structural modifications were achieved via Diels-Alder reaction 9-(2-nitrovinyl)anthracene 3-(anthracen-9-yl)-1-arylprop-2-en-1-ones (anthracene chalcones) with dienophiles, including maleic anhydride

Language: Английский

Citations

0
The role of antibody-based therapies in treating relapsed chronic lymphocytic leukemia DOI
Magdalena Witkowska, Agata Majchrzak, Paweł Robak

et al.

Expert Opinion on Biological Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Chronic lymphocytic leukemia (CLL) is one of the most common types in adult patients. The landscape CLL therapy has changed last decades with introduction antibody-based therapies and novel targeted agents resulting improved outcomes.

Language: Английский

Citations

0
Integrating pre- and post-treatment biomarkers into prognostic models for chronic lymphocytic leukemia to enhance predictive performance DOI Creative Commons
Stefano Molica

Expert Review of Molecular Diagnostics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

Language: Английский

Citations

0
Opinia ekspertów dotycząca stosowania akalabrutynibu w leczeniu przewlekłej białaczki limfocytowej DOI Open Access
Bartosz Puła, Elżbieta Iskierka‐Jażdżewska, Krzysztof Jamroziak

et al.

Published: Dec. 20, 2024

Inhibitory kinazy tyrozynowej Brutona stały się jednymi z najważniejszych leków w leczeniu pacjentów przewlekłą białaczką limfocytową (CLL). BTK są obecnie dobrze ugruntowaną terapią dla nieleczonych, jak również nawrotem lub opornych na leczenie. Wykazano, że BTKis kluczowe CLL wysokiego ryzyka aberracjami genu TP53 charakteryzujących niezmutowanym statusem regionu zmiennego łańcucha ciężkiego immunoglobulin ( IGHV ). Ibrutynib był pierwszym swojej klasie inhibitorem BTK; jednak pomimo jego potencjału terapeutycznego, charakteryzuje on określonymi działaniami niepożądanymi, tym nadciśnieniem tętniczym, zwiększonym ryzykiem krwawienia, toksycznością kardiologiczną i zmianami skórnymi. Chociaż wykazano, następna generacja jest bardziej specyficzna, ten profil zdarzeń niepożądanych uważany za specyficzny tej klasy leków. W niniejszym przeglądzie omówiono aktualny status akalabrutynibu, BTKi drugiej generacji.

Citations

0