Review
Oncology
Krish Patel, John M. Pagel
Summary: Treatment decisions for patients with chronic lymphocytic leukemia (CLL) are based on symptoms and risk classifications. New therapies targeting specific genetic aberrations have shown promising results, improving outcomes and prolonging progression-free survival. Novel targeted oral therapies have largely replaced chemoimmunotherapy in the treatment of CLL.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Immunology
Marzia Palma, Tom A. Mulder, Anders Osterborg
Summary: BTK inhibitors have revolutionized the treatment of B-cell malignancies, especially chronic lymphocytic leukemia, with three FDA-approved inhibitors and many more in development. While these inhibitors have shown promising anti-tumor effects, their off-target effects on other kinases and impact on the immune system need to be further investigated for potential clinical implications.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Hematology
Sigrid S. Skanland, Anthony R. Mato
Summary: Insight into the mechanisms of resistance to targeted therapies in chronic lymphocytic leukemia (CLL) has led to the development of strategies to prevent and overcome resistance, including combination therapies targeting bypass mechanisms, temporally sequencing of therapies, improved clinical trial designs, and real-time monitoring of patient response. These approaches aim to secure effective treatment options at the relapsed setting and overcome acquired resistance to existing therapies.
Review
Oncology
Andrew H. Lipsky, Nicole Lamanna
Summary: Targeted therapies have revolutionized the frontline treatment for CLL, reducing reliance on chemoimmunotherapy. Drugs such as ibrutinib, acalabrutinib, and venetoclax have shown efficacy in oral therapy. This review explores novel therapeutic strategies using these agents in combination, highlighting the importance of patient characteristics and study methodology.
Review
Oncology
Jing Zhang, Xueying Lu, Jianyong Li, Yi Miao
Summary: The combination of BTK inhibitors and BCL2 inhibitors in the treatment of CLL and MCL is of great clinical significance.
BIOMARKER RESEARCH
(2022)
Article
Oncology
Yanping Yin, Paschalis Athanasiadis, Linda Karlsen, Aleksandra Urban, Haifeng Xu, Ishwarya Murali, Stacey M. Fernandes, Alberto J. Arribas, Abdul K. Hilli, Kjetil Tasken, Francesco Bertoni, Anthony R. Mato, Emmanuel Normant, Jennifer R. Brown, Geir E. Tjonnfjord, Tero Aittokallio, Sigrid S. Skanland
Summary: This study analyzes the activity and cellular effects of PI3K inhibitors in CLL, finds novel treatment vulnerabilities, and suggests that ex vivo functional profiling can stratify PI3Ki responders.
CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
Bryone Kuss, Chandramouli Nagarajan, Wen Son Hsieh, Chan Yoon Cheah
Summary: The treatment of chronic lymphocytic leukemia (CLL) has improved in the past two decades with the introduction of targeted therapies. Understanding the nuances of different Bruton's tyrosine kinase (BTK) inhibitors is essential for maximizing the benefits of the next wave of these drugs.
LEUKEMIA & LYMPHOMA
(2022)
Review
Oncology
Abril Adriana Arellano-Llamas, Jorge Vela-Ojeda, Alvaro Hernandez-Caballero
Summary: Patients with CLL have a higher risk of death from COVID-19 due to inherent immunosuppression and immune deficiencies caused by treatment significantly decreasing the ability to produce natural or vaccine-induced anti-SARS-CoV-2 immune responses.
CURRENT ONCOLOGY REPORTS
(2022)
Article
Pharmacology & Pharmacy
Fanny Gallais, Loic Ysebaert, Fabien Despas, Sandra De Barros, Lucie Oberic, Ben Allal, Etienne Chatelut, Melanie White-Koning
Summary: This study developed the first PK-PD model for ALC in patients with CLL under ibrutinib treatment. The results of the model suggested that estimated lymphocyte counts in tissues and blood could be used as an early predictor of treatment response in CLL patients.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard R. Furman, Susan O'Brien, Mustafa Nuri Yenerel, Arpad Illes, Neil Kay, Jose A. Garcia-Marco, Anthony Mato, Javier Pinilla-Ibarz, John F. Seymour, Stephane Lepretre, Stephan Stilgenbauer, Tadeusz Robak, Wayne Rothbaum, Raquel Izumi, Ahmed Hamdy, Priti Patel, Kara Higgins, Sophia Sohoni, Wojciech Jurczak
Summary: In this study, acalabrutinib was found to be noninferior to ibrutinib in terms of progression-free survival in patients with CLL, with a lower incidence of cardiovascular adverse events. This suggests that acalabrutinib may be a more tolerable option for continuous therapy in this patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Fuli Fan, Hyeon Joo Yoo, Sophia Stock, Lei Wang, Yibin Liu, Maria-Luisa Schubert, Sanmei Wang, Brigitte Neuber, Angela Hueckelhoven-Krauss, Ulrike Gern, Anita Schmitt, Carsten Mueller-Tidow, Peter Dreger, Michael Schmitt, Leopold Sellner
Summary: The use of ibrutinib has been shown to improve the viability and expansion of CART cells derived from CLL patients, enriching them with less-differentiated naive-like T cell subsets and reducing exhaustion marker expression. Additionally, ibrutinib enhances the cytokine release capacity of CLL patient-derived CART cells, suggesting it can improve the yield and function of these cell products.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Max J. Gordon, Jade E. Jones, Binsah George, Christine Peterson, Jan A. Burger, Nitin Jain, Michael Keating, William G. Wierda, Jean-Bernard Durand, Alessandra Ferrajoli
Summary: This study reports the 5-year follow-up results of patients with CLL who received treatment with ibrutinib, focusing on hypertension and cardiovascular toxicities. The findings showed that although hypertension is a common side effect, it is manageable in most patients, and baseline cardiovascular disease does not affect ibrutinib-related hypertension nor is hypertension associated with major adverse cardiovascular events or survival.
Article
Health Care Sciences & Services
Javier Molina-Cerrillo, Juan Marquet-Palomanes, Teresa Alonso-Gordoa, Javier Lopez-Jimenez, Enrique Grande
Summary: COVID-19 is impacting countries worldwide, yet no approved treatment exists for SARS-CoV-2 infected patients. The virus seems to trigger an exaggerated immune response, with inflammatory cytokines like IL-6 playing a central role. Ibrutinib, known for its ability to reduce key inflammatory factors, is being explored in treating ARDS secondary to SARS-CoV-2 in patients like those with CLL.
Review
Chemistry, Medicinal
Joanna M. Rhodes, Anthony R. Mato
Summary: Understanding the B cell receptor pathway and the development of targeted BCR inhibitors, such as ibrutinib, has transformed the treatment of CLL. However, many patients discontinue treatment due to adverse events. Zanubrutinib, a second-generation BTK inhibitor, shows promising efficacy and tolerability in early phase clinical trials.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Oncology
Erika Rimondi, Elisabetta Melloni, Arianna Romani, Veronica Tisato, Fabio Casciano, Gian Matteo Rigolin, Daniela Milani, Claudio Celeghini, Giorgio Zauli, Paola Secchiero, Rebecca Voltan
Summary: The study investigates the ability of ibrutinib in combination with the MDM2-inhibitor nutlin-3 to counteract the protective effect of the tumor microenvironment in B-CLL. The combined treatment significantly increases apoptosis levels, antagonizes c-MYC up-regulation, and enhances mitochondrial apoptotic pathway components, suggesting a new therapeutic strategy to overcome drug resistance in B-CLL and potentially other cancers.
Article
Hematology
Bing Cui, Emanuela M. Ghia, Liguang Chen, Laura Z. Rassenti, Christopher DeBoever, George F. Widhopf, Jian Yu, Donna S. Neuberg, William G. Wierda, Kanti R. Rai, Neil E. Kay, Jennifer R. Brown, Jeffrey A. Jones, John G. Gribben, Kelly A. Frazer, Thomas J. Kipps
Article
Immunology
Rashmi Gupta, Xiao J. Yan, Jacqueline Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti Rai, Nicholas Chiorazzi, Patricia K. A. Mongini
JOURNAL OF IMMUNOLOGY
(2018)
Review
Oncology
Sandhya Sharma, Kanti R. Rai
Article
Immunology
Rashmi Gupta, Wentian Li, Xiao J. Yan, Jacqueline Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti Rai, Nicholas Chiorazzi, Patricia K. A. Mongini
JOURNAL OF IMMUNOLOGY
(2019)