Article
Hematology
Constantine S. Tam, John N. Allan, Tanya Siddiqi, Thomas J. Kipps, Ryan Jacobs, Stephen Opat, Paul M. Barr, Alessandra Tedeschi, Livio Trentin, Rajat Bannerji, Sharon Jackson, Bryone J. Kuss, Carol Moreno, Edith Szafer-Glusman, Kristin Russell, Cathy Zhou, Joi Ninomoto, James P. Dean, William G. Wierda, Paolo Ghia
Summary: The CAPTIVATE study is an international phase 2 study that investigated the efficacy of fixed-duration treatment with ibrutinib plus venetoclax in patients with chronic lymphocytic leukemia. The study showed promising results, with high complete response rates and durable responses, even in high-risk patients.
Article
Oncology
Karoline Kielbassa, Marco V. Haselager, Danique J. C. Bax, Bianca F. van Driel, Julie Dubois, Mark-David Levin, Sabina Kersting, Rebecka Svanberg, Carsten U. Niemann, Arnon P. Kater, Eric Eldering
Summary: Chronic lymphocytic leukemia (CLL) cells upregulate Bcl-2 proteins in the lymph node (LN) microenvironment, reducing sensitivity to the BCL-2 inhibitor venetoclax through signaling pathways involving B-cell receptor, Toll-like receptors, and CD40. A study analyzing samples from the HOVON141/VISION clinical trial found that two cycles of lead-in ibrutinib treatment decreased Bcl-2 protein expression and attenuated CD40-induced venetoclax resistance. Additionally, TLR9 stimulation reversed the effects of ibrutinib on venetoclax sensitivity by increasing CD40 expression and protein translation. These findings suggest that ibrutinib interrupts TLR9-induced CD40 upregulation, potentially inhibiting CLL cell priming for venetoclax resistance in the LN microenvironment.
Article
Oncology
Pin Lu, Shengchun Wang, Carrie A. Franzen, Girish Venkataraman, Rebecca McClure, Lei Li, Wenjun Wu, Nifang Niu, Madina Sukhanova, Jianming Pei, Donald A. Baldwin, Reza Nejati, Mariusz A. Wasik, Nadia Khan, Yifan Tu, Juehua Gao, Yihua Chen, Shuo Ma, Richard A. Larson, Y. Lynn Wang
Summary: Ibrutinib and venetoclax are effective as monotherapy for CLL, with better results when used in combination. They target different subpopulations within CLL and effectively reduce both subpopulations. Using a proliferation model may help identify novel drug combinations for eradicating residual disease.
BLOOD CANCER JOURNAL
(2021)
Article
Hematology
Matthew S. Davids, Kerry A. Rogers, Svitlana Tyekucheva, Zixu Wang, Samantha Pazienza, Sarah K. Renner, Josie Montegaard, Udochukwu Ihuoma, Timothy Z. Lehmberg, Erin M. Parry, Catherine J. Wu, Caron A. Jacobson, David C. Fisher, Philip A. Thompson, Jennifer R. Brown
Summary: In this study, we found that the oral Bcl-2 inhibitor venetoclax could increase the sensitivity of Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) to chemoimmunotherapy and improve treatment outcomes. In a single-arm trial, the combination of venetoclax and chemotherapy resulted in a 50% complete response rate, with deeper and more durable responses compared to historical regimens. Our data suggest that further studies comparing venetoclax with chemoimmunotherapy to chemoimmunotherapy alone are warranted.
Article
Oncology
Philip A. A. Thompson, Michael J. J. Keating, Alessandra Ferrajoli, Nitin Jain, Christine B. B. Peterson, Naveen Garg, Sa A. A. Wang, Jeffrey L. L. Jorgensen, Tapan M. M. Kadia, Prithviraj Bose, Naveen Pemmaraju, Nicholas J. J. Short, William G. G. Wierda
Summary: This study added venetoclax to patients who had received ibrutinib for >=12 months and had >=1 high risk feature in CLL. The results showed a high rate of U-MRD4 in the bone marrow at 12 months, suggesting a potential for durable treatment-free remission. This has important implications for patients who require long-term therapy with ibrutinib.
Article
Hematology
Craig A. Portell, Nolan A. Wages, Brad S. Kahl, Lihua E. Budde, Robert W. Chen, Jonathon B. Cohen, Nikole E. Varhegyi, Gina R. Petroni, Michael E. Williams
Summary: This study aimed to identify the optimal drug dosage combination for relapsed mantle cell lymphoma (MCL) patients. Among the 35 participants, the combination of VEN 200 mg and IBR 420 mg showed a high overall response rate (93.8%) and a low incidence of adverse reactions (6.2%). Higher dosage combinations did not improve treatment efficacy and were associated with higher toxicity.
Article
Oncology
Nitin Jain, Michael Keating, Philip Thompson, Alessandra Ferrajoli, Jan A. Burger, Gautam Borthakur, Koichi Takahashi, Zeev Estrov, Koji Sasaki, Nathan Fowler, Tapan Kadia, Marina Konopleva, Yesid Alvarado, Musa Yilmaz, Courtney DiNardo, Prithviraj Bose, Maro Ohanian, Naveen Pemmaraju, Elias Jabbour, Rashmi Kanagal-Shamanna, Keyur Patel, Wei Wang, Jeffrey Jorgensen, Sa A. Wang, Naveen Garg, Xuemei Wang, Chongjuan Wei, Nichole Cruz, Ana Ayala, William Plunkett, Hagop Kantarjian, Varsha Gandhi, William G. Wierda
Summary: The combination therapy of ibrutinib and venetoclax showed promising results in achieving bone marrow U-MRD remission in previously untreated patients with CLL. The durability of remissions was observed over a follow-up period of more than 3 years, with high response rates across different high-risk disease subgroups, including patients with del(17p)/TP53-mutated CLL.
Article
Hematology
Carol Moreno, Isabelle G. Solman, Constantine S. Tam, Andrew Grigg, Lydia Scarfo, Thomas J. Kipps, Srimathi Srinivasan, Raghuveer Singh Mali, Cathy Zhou, James P. Dean, Edith Szafer-Glusman, Michael Choi
Summary: This study evaluated immune cell subsets in patients with CLL who received different treatments. The results demonstrated successful elimination of CLL cells and restoration of normal immune cells in some patients.
Article
Hematology
Lina van der Straten, Claudia A. M. Stege, Sabina Kersting, Kazem Nasserinejad, Julie Dubois, Johan A. Dobber, Clemens H. M. Mellink, Anne-Marie F. van der Kevie-Kersemaekers, Ludo M. Evers, Fransien de Boer, Harry R. Koene, John Schreurs, Marjolein van der Klift, Gerjo A. Velders, Ellen van der Spek, Hanneke M. van der Straaten, Mels Hoogendoorn, Michel van Gelder, Eduardus F. M. Posthuma, Hein P. J. Visser, Ilse Houtenbos, Cecile A. M. Idink, Djamila E. Issa, Ellen C. Dompeling, Henk C. T. van Zaanen, J. Hendrik Veelken, Henriette Levenga, Lidwine W. Tick, Wim E. Terpstra, Sanne H. Tonino, Peter E. Westerweel, Anton W. Langerak, Arnon P. Kater, Mark-David Levin
Summary: Chronic lymphocytic leukemia (CLL) and the advanced age at diagnosis can have a negative impact on the well-being of older adult patients. Tailoring treatment to geriatric characteristics and improving health-related quality of life (HRQoL) should be a primary treatment goal. The study found that fixed-duration venetoclax plus obinutuzumab therapy improved patient-reported outcomes (PROs) and HRQoL in older, unfit patients with CLL, regardless of geriatric impairments.
Article
Hematology
Shuo Ma, John F. Seymour, Danielle M. Brander, Thomas J. Kipps, Michael Y. Choi, Mary Ann Anderson, Kathryn Humphrey, Abdullah Al Masud, John Pesko, Ruby Nandam, Ahmed Hamed Salem, Brenda Chyla, Jennifer Arzt, Amanda Jacobson, Su Young Kim, Andrew W. Roberts
Summary: The long-term follow-up of the phase 1b study of venetoclax and rituximab in patients with relapsed CLL showed durable deep responses with both continuous and limited-duration therapy. Retreatment with VenR was effective for patients experiencing disease progression after discontinuing therapy.
Article
Oncology
Amy S. Ruppert, Allison M. Booth, Wei Ding, Nancy L. Bartlett, Danielle M. Brander, Steven Coutre, Jennifer R. Brown, Sreenivasa Nattam, Richard A. Larson, Harry Erba, Mark Litzow, Carolyn Owen, Charles S. Kuzma, Jeremy S. Abramson, Richard F. Little, Scott E. Smith, Richard M. Stone, John C. Byrd, Sumithra J. Mandrekar, Jennifer A. Woyach
Summary: Ibrutinib shows better progression-free survival compared to bendamustine plus rituximab in older CLL patients, but differences in treatment duration and cycles make adverse event comparisons complicated. The AE burden score (AE(sc)) helps to compare and characterize adverse events over time for both treatment options.
Article
Oncology
Michael Wang, Radhakrishnan Ramchandren, Robert Chen, Lionel Karlin, Geoffrey Chong, Wojciech Jurczak, Ka Lung Wu, Mark Bishton, Graham P. Collins, Paul Eliadis, Frederic Peyrade, Yihua Lee, Karl Eckert, Jutta K. Neuenburg, Constantine S. Tam
Summary: Ibrutinib plus venetoclax has shown promising clinical activity in mantle cell lymphoma patients, with concurrent administration without an ibrutinib lead-in. The overall response rate was 81% and complete response rate was 62%, with no new safety signals observed in the safety run-in cohort.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
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)
Review
Oncology
Md. Khirul Islam, Misba Khan, Kamlesh Gidwani, Kenneth W. Witwer, Urpo Lamminmaeki, Janne Leivo
Summary: Extracellular vesicles (EVs) have potential as diagnostic, prognostic, and therapeutic agents for cancer. The glycosylation patterns on the EV surface can reveal their cell of origin and be used for targeted delivery. Lectins and other glycan recognizing entities can be powerful tools for discovering and detecting novel cancer biomarkers.
BIOMARKER RESEARCH
(2023)
Article
Oncology
Andrea Visentin, Francesca Romana Mauro, Gioachino Catania, Alberto Fresa, Candida Vitale, Alessandro Sanna, Veronica Mattiello, Francesca Cibien, Paolo Sportoletti, Massimo Gentile, Gian Matteo Rigolin, Francesca Maria Quaglia, Roberta Murru, Alessandro Gozzetti, Stefano Molica, Monia Marchetti, Stefano Pravato, Francesco Angotzi, Alessandro Cellini, Lydia Scarfo, Gianluigi Reda, Marta Coscia, Luca Laurenti, Paolo Ghia, Robin Foa, Antonio Cuneo, Livio Trentin
Summary: The study compared continuous or fixed-duration therapy in patients with chronic lymphocytic leukemia (CLL). The results showed that continuous use of ibrutinib (IB) provided better disease control in CLL patients, but fixed-duration obinutuzumab-based treatment (G-CHL) showed significant clinical and economic benefits in IGHV mutated patients and patients achieving undetectable measurable residual disease.
FRONTIERS IN ONCOLOGY
(2022)
Article
Clinical Neurology
Marton Konig, Aslaug Rudjord Lorentzen, Hilde Marie Torgauten, The Trung Tran, Stine Schikora-Rustad, Eline Benno Vaage, Ase Mygland, Stig Wergeland, Jan Aarseth, Ingeborg Aase S. Aaberge, Oivind Torkildsen, Trygve Holmoy, Tone Berge, Kjell-Morten Myhr, Hanne Flinstad Harbo, Jan Terje Andersen, Ludvig Andre Munthe, Arne Soraas, Elisabeth Gulowsen Celius, John Torgils Vaage, Fridtjof Lund-Johansen, Gro Owren Nygaard
Summary: This study aimed to characterize humoral immunity after mRNA-COVID-19 vaccination in people with multiple sclerosis (pwMS). The study found that patients treated with fingolimod or rituximab had reduced humoral immunity. It is important to carefully time the vaccinations for patients treated with rituximab.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Editorial Material
Hematology
Sigrid S. Skanland, Marit Inngjerdingen, Henrik Bendiksen, Jamie York, Signe Spetalen, Ludvig A. Munthe, Geir E. Tjonnfjord
Review
Hematology
Sigrid S. Skanland, Jennifer R. Brown
Summary: Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown efficacy in CLL, but their use is limited due to severe toxicity and availability of more tolerable agents. Optimizing the administration of current PI3K inhibitors and developing next-generation agents is important to improve tolerability. Strategies to overcome limitations include intermittent dosing and combination with other agents, as well as identifying biomarkers to personalize treatment decisions.
Review
Biochemistry & Molecular Biology
Kanganwiro Mugwanda, Saltiel Hamese, Winschau F. Van Zyl, Earl Prinsloo, Morne Du Plessis, Leon M. T. Dicks, Deepak B. Thimiri Govinda Raj
Summary: Synthetic biology has experienced rapid growth in the field of biology, and one emerging application is the utilization of microorganisms to improve human health. Selecting appropriate synthetic biology tools for specific microorganisms is critical for addressing unmet medical needs. Lactic acid bacteria, which can be genetically engineered, are considered suitable for therapeutic and industrial applications.
BIOSCIENCE REPORTS
(2023)
Article
Hematology
Deyi Zhang, Hailey M. Harris, Jonathan Chen, Jen Judy, Gabriella James, Aileen Kelly, Joel McIntosh, Austin Tenn-McClellan, Eileen Ambing, Ying Siow Tan, Hao Lu, Stefan Gajewski, Matthew C. Clifton, Stephanie Yung, Daniel W. Robbins, Mehdi Pirooznia, Sigrid S. Skanland, Erika Gaglione, Maissa Mhibik, Chingiz Underbayev, Inhye E. Ahn, Clare Sun, Sarah E. M. Herman, Mark Noviski, Adrian Wiestner
Summary: BTK is crucial for CLL signaling and covalent inhibitors have been commonly used. However, resistance due to C481 mutations is common. NRX-0492, a noncovalent BTK degrader, effectively degrades both wild-type and C481 mutant BTK, providing a potential solution for overcoming BTK inhibitor resistance.
Article
Rheumatology
Kristin H. Bjorlykke, Hilde S. orbo, Anne Tveter, Ingrid Jyssum, Joseph Sexton, Trung Tran, Ingrid E. Christensen, Grete Birkeland Kro, Tore K. Kvien, Jorgen Jahnsen, Ludvig A. Munthe, Adity Chopra, David J. Warren, Siri Mjaaland, Espen A. Haavardsholm, Gunnveig Grodeland, Sella A. Provan, John T. Vaage, Silje Watterdal Syversen, Guro Lovik Goll, Kristin Kaasen Jorgensen
Summary: This study aimed to evaluate hybrid immunity and humoral immune response and safety of four SARS-CoV-2 vaccine doses in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. The results showed that vaccine boosters improve humoral immune responses and are safe in patients with immune-mediated inflammatory diseases on immunosuppressive therapy.
LANCET RHEUMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Asia-Sophia Wolf, Anthony Ravussin, Marton Konig, Mathias H. Overas, Guri Solum, Ingrid Fadum Kjonstad, Adity Chopra, Trygve Holmoy, Hanne F. Harbo, Silje Watterdal Syversen, Kristin Kaasen Jorgensen, Einar August Hogestol, Jon Torgils Vaage, Elisabeth G. Celius, Fridtjof Lund-Johansen, Ludvig A. Munthe, Gro Owren Nygaard, Siri Mjaaland
Summary: This study investigates the immune responses of people with multiple sclerosis receiving disease-modifying therapies (DMTs) to COVID-19 vaccination. The study finds that lymphocyte-targeting immunotherapies attenuate antibody responses, and thus, evaluating cellular responses after vaccination is crucial. The results show that although pwMS receiving rituximab and fingolimod therapies had low antibody responses, T cell responses in pwMS taking rituximab were preserved after a third vaccination. PwMS taking fingolimod had low detectable T cell responses in peripheral blood, and T cell responses to SARS-CoV-2 variants Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. These findings highlight the importance of assessing both cellular and humoral responses after vaccination in pwMS and suggest that vaccination can generate immune responses even in the absence of robust antibody responses.
Article
Cell Biology
Johanne U. Hermansen, Yanping Yin, Aleksandra Urban, Camilla V. Myklebust, Linda Karlsen, Katrine Melvold, Anders A. Tveita, Kjetil Tasken, Ludvig A. Munthe, Geir E. Tjonnfjord, Sigrid S. Skanland
Summary: The microenvironment of CLL cells plays a crucial role in their survival, proliferation, and drug resistance. A model has been developed that can replicate this microenvironment and is compatible with drug sensitivity screens. This model has been used to identify treatment vulnerabilities and guide precision medicine for CLL patients.
CELL DEATH DISCOVERY
(2023)
Article
Immunology
Lorenzo Federico, Tor Henrik Anderson Tvedt, Murat Gainullin, Julie Rokke Osen, Viktoriia Chaban, Katrine Persgard Lund, Lisa Tietze, Trung The Tran, Fridtjof Lund-Johansen, Hassen Kared, Andreas Lind, John Torgils Vaage, Richard Stratford, Simen Tennoe, Brandon Malone, Trevor Clancy, Anders Eivind Leren Myhre, Tobias Gedde-Dahl, Ludvig Andre Munthe
Summary: This study examined the relationship between humoral and T cell response in 48 HSCT recipients who received two doses of Moderna's mRNA-1273 or Pfizer/BioNTech's BNT162b2 vaccines. The results showed that nearly all HSCT patients had robust T cell immunity regardless of protective humoral responses. The data suggests that HSCT recipients with poor serological responses were protected from severe COVID-19 by vaccine-induced T cell responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Geriatrics & Gerontology
Anthony Ravussin, Anna Hayman Robertson, Asia -Sophia Wolf, Kristine Blix, Ingrid Fadum Kjonstad, Guri Solum, Berit Feiring, Bjorn Heine Strand, Fridtjof Lund-Johansen, Ludvig A. Munthe, Per Magnus, Lill Trogstad, Siri Mjaaland
Summary: The Norwegian Institute of Public Health established a longitudinal cohort study to investigate the effects of COVID-19 on older adults aged 65-80. They analyzed the characteristics of the cohort and examined the immune responses before and after vaccination, as well as the factors affecting these responses.
LANCET HEALTHY LONGEVITY
(2023)
Article
Cell Biology
Pilar Ayuda-Duran, Johanne U. Hermansen, Mariaserena Giliberto, Yanping Yin, Robert Hanes, Sandra Gordon, Heikki Kuusanmaki, Andrea M. Brodersen, Aram N. Andersen, Kjetil Tasken, Krister Wennerberg, Jorrit M. Enserink, Sigrid S. Skanland
Summary: The principle of drug sensitivity testing is important for the diagnosis and treatment of patients with hematologic cancers. Optimized protocols for culturing and drug screening are necessary to ensure accurate reflection of in vivo drug responses. This article provides protocols for AML, CLL, and MM patients and discusses drug library designs and quality controls.
CELL DEATH DISCOVERY
(2023)
Review
Biotechnology & Applied Microbiology
Saltiel Hamese, Kanganwiro Mugwanda, Mutsa Takundwa, Earl Prinsloo, Deepak B. Thimiri Govinda Raj
Summary: This article provides an overview of microbial host selection, synthetic biology, genome annotation, metabolic modeling, and computational methods for predicting gene essentiality for developing a microbial chassis. It focuses on lactic acid bacteria (LAB) as a microbial chassis and strategies for genome annotation. The article also discusses insights into streamlining genome reduction without compromising the functionality of the chassis and the potential for minimal genome chassis development.
JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Immunology
Lorenzo Federico, Brandon Malone, Simen Tennoe, Viktoriia Chaban, Julie Rokke Osen, Murat Gainullin, Eva Smorodina, Hassen Kared, Rahmad Akbar, Victor Greiff, Richard Stratford, Trevor Clancy, Ludvig Andre Munthe
Summary: In this study, an AI-driven tool called NEC Immune Profiler (NIP) was used to predict T cell immunogenic regions from the entire SARS-CoV-2 viral proteome. T cell responses to these predicted epitopes were validated and characterized, showing the accuracy of AI platforms in predicting immunogenicity. The findings provide a new framework for evaluating vaccine-induced T cell responses.
FRONTIERS IN IMMUNOLOGY
(2023)