Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
John N. Allan, Ian W. Flinn, Tanya Siddiqi, Paolo Ghia, Constantine S. Tam, Thomas J. Kipps, Paul M. Barr, Anna Elinder Camburn, Alessandra Tedeschi, Xavier C. Badoux, Ryan Jacobs, Bryone J. Kuss, Livio Trentin, Cathy Zhou, Anita Szoke, Christopher Abbazio, William G. Wierda
Summary: The CAPTIVATE study demonstrates that fixed-duration ibrutinib plus venetoclax is effective in controlling chronic lymphocytic leukemia, including patients with high-risk genomic features. This treatment provides durable progression-free survival and similar overall survival rates.
CLINICAL CANCER RESEARCH
(2023)
Editorial Material
Hematology
Barbara Eichhorst
Summary: In this study, Shanafelt et al confirm the continued superiority of ibrutinib plus rituximab (IR) over the prior standard treatment for fit patients with CLL. They also provide important data on the tolerability of continuous treatment with BTK inhibitor.
Editorial Material
Hematology
Thomas E. Lew, Constantine S. Tam, John F. Seymour
Summary: Venetoclax-based regimens have improved therapeutic options for CLL patients, achieving remissions without chemotherapy. However, long-term follow-up reveals frequent disease resistance and progression in patients with TP53 aberrations.
Article
Medicine, General & Internal
Martin Simkovic, Pavel Vodarek, Monika Motyckova, Dominika ecsiova, Petra Rozsivalova, Heidi Mocikova, Pavla Stepankova, Alice Sykorova, Katerina Hrochova, Filip Vrbacky, David Belada, Pavel Zak, Lukas Smolej
Summary: The RCD regimen is an effective treatment option for elderly patients with relapsed CLL, with significant predictors of shorter PFS being TP53 deletion/mutation, advanced Rai stage, and >= 2 previous lines of treatment. The addition of cyclophosphamide to the R-Dex regimen maintains similar efficacy, even with a 50% reduction in the dexamethasone dose.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Biochemistry & Molecular Biology
Nawar Maher, Samir Mouhssine, Bassam Francis Matti, Alaa Fadhil Alwan, Gianluca Gaidano
Summary: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Chemoimmunotherapy (CIT) was the commonest option for CLL treatment, but resistance to CIT has led to the use of targeted pathway inhibitors such as BTK and BCL2 inhibitors. However, acquired genetic lesions can cause resistance to these inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Remi Letestu, Abdelmalek Dahmani, Marouane Boubaya, Lucile Baseggio, Lydia Campos, Bernard Chatelain, Agathe Debliquis, Bernard Drenou, Marie-Christine Jacob, Eric Legac, Magali Le Garff-Tavernier, Anne-Catherine Lhoumeau, Claire Quiney, Nelly Robillard, Michel Ticchioni, Carmen Aanei, Sandrine Katsahian, Roselyne Delepine, Sandrine Vaudaux, Valerie Rouille, Marie-Christine Bene, Caroline Dartigeas, Eric van den Neste, Stephane Lepretre, Pierre Feugier, Guillaume Cartron, Veronique Leblond, Vincent Levy, Florence Cymbalista
Summary: High-sensitivity MRD assessment in patients with chronic lymphocytic leukemia can provide additional prognostic information, with low-level positive MRD in blood associated with longer progression-free survival, but not in bone marrow.
Article
Hematology
Yair Herishanu, Irit Avivi, Anat Aharon, Gabi Shefer, Shai Levi, Yotam Bronstein, Miguel Morales, Tomer Ziv, Yamit Shorer Arbel, Lydia Scarfo, Erel Joffe, Chava Perry, Paolo Ghia
Summary: Patients with chronic lymphocytic leukemia have a significantly impaired antibody response to the BNT162b2 mRNA COVID-19 vaccine, which is influenced by disease activity and treatment.
Article
Cell Biology
Chi-Ling Chiang, Eileen Y. Hu, Lingqian Chang, Jadwiga Labanowska, Kevan Zapolnik, Xiaokui Mo, Junfeng Shi, Tzyy-Jye Doong, Arletta Lozanski, Pearlly S. Yan, Ralf Bundschuh, Logan A. Walker, Daniel Gallego-Perez, Wu Lu, Meixiao Long, Sanggu Kim, Nyla A. Heerema, Gerard Lozanski, Jennifer A. Woyach, John C. Byrd, Ly James Lee, Natarajan Muthusamy
Summary: This study used a microchannel electroporation technique to investigate the hematopoietic stem cells in chronic lymphocytic leukemia, confirming the existence of clonal hematopoietic stem cells and their differential drug sensitivity. Furthermore, the existence of CLL LICs was validated in both patient and mouse models. Additionally, differential protein ubiquitination and unfolding response were found in GATA2(high) CLL-HSCs, which significantly affected drug sensitivity.
Article
Oncology
Maria Joao Baptista, Sivasubramanian Baskar, Erika M. Gaglione, Keyvan Keyvanfar, Inhye E. Ahn, Adrian Wiestner, Clare Sun
Summary: In CLL patients, Ibrutinib treatment increases clonality of the TCR repertoire, with stable TCR clonality in patients with sustained remission and decreased TCR clonality in patients with disease progression. Additionally, T cells from responding patients show cytotoxicity against autologous CLL cells in vitro.
CLINICAL CANCER RESEARCH
(2021)
Review
Medicine, General & Internal
Mazyar Shadman
Summary: Chronic lymphocytic leukemia is an immunocompromised blood cancer that can be treated with targeted agents like BTK inhibitors or BCL2 inhibitors, but currently there is no cure for the disease.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Oncology
Peter Hillmen, Alexandra Pitchford, Adrian Bloor, Angus Broom, Moya Young, Ben Kennedy, Renata Walewska, Michelle Furtado, Gavin Preston, Jeffrey R. Neilson, Nicholas Pemberton, Gamal Sidra, Nicholas Morley, Kate Cwynarski, Anna Schuh, Francesco Forconi, Nagah Elmusharaf, Shankara Paneesha, Christopher P. Fox, Dena R. Howard, Anna Hockaday, Julia M. Brown, David A. Cairns, Sharon Jackson, Natasha Greatorex, Nichola Webster, Jane Shingles, Surita Dalal, Piers E. M. Patten, David Allsup, Andrew Rawstron, Talha Munir
Summary: This study compares the efficacy of ibrutinib and rituximab with fludarabine, cyclophosphamide, and rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients. The results show that ibrutinib and rituximab significantly improve progression-free survival compared to the standard chemoimmunotherapy.
Article
Oncology
Paul J. Hampel, Kari G. Rabe, Timothy G. Call, Wei Ding, Jose F. Leis, Asher A. Chanan-Khan, Saad S. Kenderian, Eli Muchtar, Yucai Wang, Sikander Ailawadhi, Amber B. Koehler, Ricardo Parrondo, Susan M. Schwager, Taimur Sher, Curtis A. Hanson, Min Shi, Daniel L. Van Dyke, Esteban Braggio, Susan L. Slager, Neil E. Kay, Sameer A. Parikh
Summary: Patients with chronic lymphocytic leukemia (CLL) who have disease progression on ibrutinib have worse outcomes compared to those who stop ibrutinib due to toxicity. A study evaluated the outcomes of CLL patients with disease progression on ibrutinib and found that overall survival (OS) was longer for patients who received ibrutinib as a frontline treatment and next-line treatments such as chimeric antigen receptor T-cell therapy and venetoclax-based treatment showed better outcomes compared to other approved treatments. These findings suggest a need for better treatment options for CLL patients with disease progression on ibrutinib.
BLOOD CANCER JOURNAL
(2022)
Review
Oncology
Lukas Smolej, Pavel Vodarek, Dominika Ecsiova, Martin Simkovic
Summary: Chemotherapy combined with immunotherapy has been a mainstay in the first-line treatment of chronic lymphocytic leukaemia, but is now being replaced by oral targeted inhibitors due to their superior efficacy in prolonging progression-free survival. However, these inhibitors come with disadvantages such as specific side effects, long-term therapy requirements, and high cost, highlighting the need to identify patients who may still benefit from chemoimmunotherapy.
Article
Hematology
Petra Langerbeins, Can Zhang, Sandra Robrecht, Paula Cramer, Moritz Fuerstenau, Othman Al-Sawaf, Julia von Tresckow, Anna-Maria Fink, Karl-Anton Kreuzer, Ursula Vehling-Kaiser, Eugen Tausch, Lothar Mueller, Michael Josef Eckart, Rudolf Schlag, Werner Freier, Tobias Gaska, Christina Balser, Marcel Reiser, Martina Stauch, Clemens-Martin Wendtner, Kirsten Fischer, Stephan Stilgenbauer, Barbara Eichhorst, Michael Hallek
Summary: Observation is the standard of care for early-stage asymptomatic chronic lymphocytic leukemia (CLL) patients, as chemotherapy-based interventions have not been effective in prolonging survival. However, early intervention with ibrutinib may lead to superior disease control and is well tolerated. The CLL12 trial showed that ibrutinib significantly improved event-free survival in asymptomatic, treatment-naive early-stage CLL patients at increased risk of progression, without increasing overall toxicity.