Article
Oncology
Irene Dogliotti, Cristina Jimenez, Marzia Varettoni, Dipti Talaulikar, Tina Bagratuni, Martina Ferrante, Jose Perez, Daniela Drandi, Noemi Puig, Milena Gilestro, Maria Garcia-Alvarez, Roger Owen, Wojciech Jurczak, Alessandra Tedeschi, Veronique Leblond, Efstathios Kastritis, Marie Jose Kersten, Shirley D'Sa, Michal Kascak, Wolfgang Willenbacher, Aldo M. Roccaro, Stephanie Poulain, Pierre Morel, Charalampia Kyriakou, Falko Fend, Josephine M. Vos, Meletios A. Dimopoulos, Christian Buske, Simone Ferrero, Ramon Garcia-Sanz
Summary: This paper presents consensus recommendations and laboratory requirements for the diagnosis of Waldenstrom's macroglobulinemia (WM) developed by the European Consortium of Waldenstrom's Macroglobulinemia, providing guidance for clinicians and researchers on multiparametric flow cytometry, fluorescence in situ hybridization, and molecular tests.
Article
Multidisciplinary Sciences
Kelsie J. Anson, Giulia A. Corbet, Amy E. Palmer
Summary: In this study, the researchers investigated how changes in intracellular zinc ion levels affect kinase signaling pathways using fluorescent biosensors and cell perturbations. The results showed that zinc ion fluctuations are not toxic and do not activate stress-dependent kinase signaling. Additionally, the study demonstrated that while zinc ions can inhibit phosphatases, ERK and Akt are primarily activated through upstream signaling pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Christian Buske, Alessandra Tedeschi, Judith Trotman, Ramon Garcia-Sanz, David MacDonald, Veronique Leblond, Beatrice Mahe, Charles Herbaux, Jeffrey V. Matous, Constantine S. Tam, Leonard T. Heffner, Marzia Varettoni, M. Lia Palomba, Chaim Shustik, Efstathios Kastritis, Steven P. Treon, Jerry Ping, Bernhard Hauns, Israel Arango-Hisijara, Meletios A. Dimopoulos
Summary: The final analysis of the iNNOVATE study demonstrated that ibrutinib-rituximab maintained sustained efficacy in patients with WM, regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Hematology
Daphne Krzisch, Nayara Guedes, Clementine Boccon-Gibod, Marine Baron, Clotilde Bravetti, Frederic Davi, Marine Armand, Luce Smagghe, Jonathan Caron, Olivier A. Bernard, Santos Susin, Elise Chapiro, Veronique Leblond, Florence Nguyen-Khac, Damien Roos-Weil
Summary: In Waldenstrom macroglobulinemia (WM), MYD88 mutation is common among patients, but clinical presentation and treatment response can vary greatly. Cytogenetic and molecular abnormalities did not significantly affect initial treatment and response, but were significantly associated with PFS and OS. Integration of both cytogenetic and molecular screening is recommended for evaluating first-line WM patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Hematology
Steven P. Treon, Kirsten Meid, Zachary R. Hunter, Catherine A. Flynn, Shayna R. Sarosiek, Carly R. Leventoff, Timothy P. White, Yang Cao, Aldo M. Roccaro, Antonio Sacco, Maria G. Demos, Maria Luisa Guerrera, Amanda Kofides, Xia Liu, Lian Xu, Christopher J. Patterson, Manit Munshi, Nicholas Tsakmaklis, Guang Yang, Irene M. Ghobrial, Andrew R. Branagan, Jorge J. Castillo
Summary: The study examined the combination of CXCR4-antagonist ulocuplumab and ibrutinib in treating WM patients, demonstrating promising clinical efficacy and survival outcomes.
Article
Oncology
Steven P. Treon, Kirsten Meid, Joshua Gustine, Guang Yang, Lian Xu, Xia Liu, Christopher J. Patterson, Zachary R. Hunter, Andrew R. Branagan, Jacob P. Laubach, Irene M. Ghobrial, M. Lia Palomba, Ranjana Advani, Jorge J. Castillo
Summary: In this study, the long-term and final analysis of ibrutinib monotherapy in previously treated patients with WM showed promising results in disease control. Response to treatment was impacted by mutation status of MYD88 and CXCR4, with MYD88(Mut)CXCR4(WT) patients demonstrating higher progression-free survival rates. Treatment with ibrutinib was well-tolerated with manageable adverse events.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Magdalini Migkou, Despina Fotiou, Maria Gavriatopoulou, Meletios Athanasios Dimopoulos
Summary: Waldenstrom's macroglobulinemia (WM) is a rare disease with unique clinical features, and rituximab is commonly used in treatment, but the introduction of ibrutinib has changed the landscape. Although the combination therapy is effective and safe, challenges remain in long-term treatment, and further research is needed to establish the optimal therapeutic approach.
EXPERT OPINION ON DRUG SAFETY
(2021)
Article
Hematology
Joshua N. Gustine, Shayna Sarosiek, Catherine A. Flynn, Kirsten Meid, Carly Leventoff, Timothy White, Maria Luisa Guerrera, Lian Xu, Amanda Kofides, Nicholas Tsakmaklis, Manit Munshi, Maria Demos, Christopher J. Patterson, Xia Liu, Guang Yang, Zachary R. Hunter, Andrew R. Branagan, Steven P. Treon, Jorge J. Castillo
Summary: Continuation of ibrutinib until subsequent treatment is associated with improved disease control and clinical outcomes in patients with acquired resistance to ibrutinib monotherapy for Waldenstrom macroglobulinemia.
Article
Multidisciplinary Sciences
Ravi Varma Aithabathula, Naveed Pervaiz, Ishita Kathuria, Mallory Swanson, Udai P. Singh, Santosh Kumar, Frank Park, Bhupesh Singla
Summary: This study demonstrates the potential role of H2S donor NaHS in promoting lymphatic vessel formation, suggesting its potential for treating lymphatic dysfunction-related disorders.
Article
Oncology
Christian Buske, Alessandra Tedeschi, Judith Trotman, Ramon Garcia-Sanz, David MacDonald, Veronique Leblond, Beatrice Mahe, Charles Herbaux, Jeffrey Matous, Constantine S. Tam, Leonard T. Heffner, Marzia Varettoni, M. Lia Palomba, Chaim Shustik, Efstathios Kastritis, Steven P. Treon, Jerry Ping, Bernhard Hauns, Israel Arango-Hisijara, Meletios A. Dimopoulos
Summary: This article summarizes the 5-year results of the iNNOVATE trial, which compared the effectiveness of ibrutinib plus rituximab to rituximab alone in patients with Waldenstrom's macroglobulinemia. The results showed that ibrutinib plus rituximab led to improved disease outcomes and longer progression-free survival compared to placebo plus rituximab. Side effects were manageable and decreased over time. The study also found that ibrutinib plus rituximab significantly improved quality of life for patients.
Article
Cell Biology
Srinivas Animireddy, Padmavathi Kavadipula, Viswakalyan Kotapalli, Swarnalata Gowrishankar, Satish Rao, Murali Dharan Bashyam
Summary: The ARID1B subunit of the SWI/SNF chromatin remodeling complex functions as a nuclear tumor suppressor, but cytoplasmic localization of ARID1B may lead to gain-of-function oncogenic properties through specific signaling pathways.
JOURNAL OF CELL SCIENCE
(2021)
Article
Oncology
Xufen Ding, Tianwei Chen, Qian Shi, Peng Nan, Xiang Wang, Dong Xie, Jingjing Li
Summary: INTS6 has been found to be overexpressed in colorectal cancer (CRC) tissues, and its downregulation can induce cell cycle arrest and inhibit the growth of CRC cells and tumors. The oncogenic role of INTS6 in CRC has been revealed, providing a potential therapeutic target for this malignant cancer.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Hematology
Jorge J. Castillo, Shayna R. Sarosiek, Joshua N. Gustine, Catherine A. Flynn, Carly R. Leventoff, Timothy P. White, Kirsten Meid, Maria L. Guerrera, Amanda Kofides, Xia Liu, Manit Munshi, Nicholas Tsakmaklis, Zachary R. Hunter, Christopher J. Patterson, Andrew R. Branagan, Steven P. Treon
Summary: This study confirms the predictive and prognostic value of CXCR4 mutations in patients with Waldenstroeurom macroglobulinemia (WM) treated with ibrutinib monotherapy.
Article
Biochemistry & Molecular Biology
Wangjie Jiang, Xiao Yang, Kuangheng Shi, Yaodong Zhang, Xiaoli Shi, Jifei Wang, Yuming Wang, Anlan Chenyan, Jijun Shan, Yirui Wang, Jiang Chang, Ruixiang Chen, Tao Zhou, Yanping Zhu, Yue Yu, Changxian Li, Xiangcheng Li
Summary: In cholangiocarcinoma, up-regulated MAD2 promotes cancer progression and lymphatic metastasis through the USP44/LIMA1/PI3K/AKT pathway.
Article
Biochemistry & Molecular Biology
Santino Blando, Ivana Raffaele, Luigi Chiricosta, Andrea Valeri, Agnese Gugliandolo, Serena Silvestro, Federica Pollastro, Emanuela Mazzon
Summary: This study investigates the effect of cannabidiol (CBD) on neuronal differentiation at different concentrations and reveals a potential correlation between CBD, neurodifferentiation, and retinoic acid receptor-related orphan receptors (RORs).
Review
Hematology
Jorge J. Castillo, Christian Buske, Judith Trotman, Shayna Sarosiek, Steven P. Treon
Summary: BTK inhibitors play a crucial role in the treatment of Waldenstrom macroglobulinemia, being the only FDA-approved agents for these patients. However, there are still unmet needs with BTK inhibitor therapy, such as indefinite duration therapy, high cost, scarcity of complete responses, and lower response rates in patients with CXCR4 mutations. This review focuses on the data supporting the use of covalent BTK inhibitors, management issues, clinical trials with covalent BTK inhibitor combination regimens, and upcoming non-covalent BTK inhibitors.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Shayna Sarosiek, Joshua N. N. Gustine, Catherine A. A. Flynn, Carly Leventoff, Megan Little, Timothy White, Kirsten Meid, Steven P. P. Treon, Jorge J. J. Castillo
Summary: Waldenstrom macroglobulinaemia (WM) is a type of blood cancer with a specific mutation known as MYD88(L265P). This mutation activates the Bruton tyrosine kinase (BTK), promoting the growth and survival of malignant cells. Ibrutinib is a BTK inhibitor approved for the treatment of WM. However, the impact of reducing the dosage of ibrutinib has not been extensively studied.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Danka Cholujova, Gabor Beke, Zachary R. Hunter, Teru Hideshima, Ludmila Flores, Tatiana Zeleznikova, Denisa Harrachova, Lubos Klucar, Merav Leiba, Lubos Drgona, Steven P. Treon, Efstathios Kastritis, David M. Dorfman, Kenneth C. Anderson, Jana Jakubikova
Summary: By using mass cytometry, this study characterized the immunophenotypic changes in Waldenstrom macroglobulinemia (WM) and revealed the modulation of immune cells by immune checkpoints. It was found that the response to treatment strategies in WM can be monitored by observing the changes in immune cells.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Shayna Sarosiek, Jorge J. Castillo
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
(2023)
Article
Oncology
Denisse Castro, Bryan Valcarcel, Thanya Runciman, Yesenia Huerta-Collado, Sally Paredes, Brady E. Beltran, Jorge J. Castillo, Luis Malpica
Summary: We evaluated the effect of high red distribution width-coefficient of variation (RDW-CV) values (>14%) on all-cause and lymphoma-specific mortality outcomes among 118 patients with peripheral T-cell lymphoma (PTCL). Results showed that patients with a high RDW-CV had a lower overall survival rate and a higher cumulative incidence of lymphoma mortality. RDW-CV emerges as an easily accessible and complementary prognostic biomarker for risk stratification among treated patients with de novo PTCL.
LEUKEMIA & LYMPHOMA
(2023)
Article
Hematology
Steven P. Treona, Alessandra Tedeschi, Jesus San-Miguel, Ramon Garcia-Sanz, Kenneth C. Anderson, Eva Kimby, Monique C. Minnema, Giulia Benevolo, Lugui Qiu, Shuhui Yi, Evangelos Terpos, Constantine S. Tam, Jorge J. Castillo, Pierre Morel, Meletios Dimopoulos, Roger G. Owen
Summary: The consensus panel reviewed the current criteria for diagnosis and response assessment of Waldenstrom's Macroglobulinemia. The key recommendations included reaffirming the previous consensus panel's recommendation to not use arbitrary values for laboratory parameters to distinguish between Waldenstrom's Macroglobulinemia and IgM MGUS, delineating IgM MGUS into two subclasses, and recognizing simplified response assessments using serum IgM levels.
SEMINARS IN HEMATOLOGY
(2023)
Article
Hematology
Christian Buskea, Jorge J. Castillo, Jithma Prasad Abeykoonc, Ranjana Advanid, Suzanne O. Arulogune, Andrew R. Branaganf, Xinxin Caog, Shirley D'Sae, Jian Houh, Prashant Kapoorc, Efstathios Kastritisi, Marie J. Kerstenj, Veronique LeBlondk, Merav Leibal, Jeffrey V. Matous, Jonas Paludo, Lugui Qiu, Constantine S. Tam, Alessandra Tedeschi, Sheeba K. Thomas, Ibrahim Tohidi-Esfahani, Marzia Varettonis, Josephine M. Vosj, Ramon Garcia-Sanz, Jesus San-Miguel, Meletios A. Dimopoulos, Steven P. Treon, Judith Trotmanr
Summary: The consensus panel recommends watchful waiting for asymptomatic patients, and chemoimmunotherapy (CIT) regimens or covalent BTK inhibitors (cBTKi) for first-line treatment of symptomatic patients. The mutational status of MYD88 and CXCR4 should be determined before treatment initiation. Treatment approaches for WM-associated complications aim to reduce tumor burden and abnormal protein levels. Patients' participation in clinical trials is crucial for the continuous improvement of treatment options.
SEMINARS IN HEMATOLOGY
(2023)
Article
Hematology
S. D'Sa, J. Matous, R. Advani, C. Buske, J. J. Castillo, M. Gatt, P. Kapoor, M. J. Kersten, V Leblond, M. Leiba, M. L. Palomba, J. Paludo, L. Qiu, S. Sarosiek, M. Shadman, D. Talaulikar, C. S. Tam, A. Tedeschi, S. K. Thomas, I Tohidi-Esfahani, J. Trotman, M. Varettoni, J. M. Vos, R. Garcia-Sanz, J. San-Miguel, M. A. Dimopoulos, S. P. Treon, E. Kastritis
Summary: The consensus panel 2 (CP2) of the 11th International Workshop on Waldenstrom's macroglobulinemia (IWWM-11) updated the recommendations for treating patients with relapsed or refractory WM (RRWM) based on current data. The key recommendations include considering chemoimmunotherapy and/or covalent Bruton tyrosine kinase strategies, taking into account patient characteristics, disease phenotype, mutational status, and toxicities. After BTKi failure, various treatment options such as different CIT regimens, addition of anti-CD20 antibody, and newer BTKi or non-covalent BTKi can be considered. Participation in clinical trials should be encouraged.
SEMINARS IN HEMATOLOGY
(2023)
Article
Hematology
C. S. Tam, P. Kapoor, J. J. Castillo, C. Buske, S. M. Ansell, A. R. Branagan, E. Kimby, Y. Li, M. L. Palomba, L. Qiu, M. Shadman, J. P. Abeykoon, S. Sarosiek, J. M. Vos, S. Yi, D. Stephens, D. Roos-Weil, A. M. Roccaro, P. Morel, N. C. Munshi, K. C. Anderson, J. San-Miguel, R. Garcia-Sanz, M. A. Dimopoulos, S. P. Treon, M. J. Kersten
Summary: Recent advances in understanding WM biology have influenced the development of novel agents and improved knowledge of WM genomics. CP7 examined completed and ongoing clinical trials and made recommendations for future trials, prioritizing limited duration and novel agent combinations. Evaluating MYD88, CXCR4, and TP53 at baseline and using bendamustine-rituximab or dexamethasone, rituximab and cyclophosphamide as standard treatments were suggested. Unanswered questions include defining frailty, determining the importance of achieving VGPR within a specific time frame, and providing optimal treatment for WM populations with special needs.
SEMINARS IN HEMATOLOGY
(2023)
Article
Hematology
Ramon Garcia-Sanz, Marzia Varettoni, Cristina Jimenez, Simone Ferrero, Stephanie Poulain, Jesus F. San-Miguel, Maria L. Guerrera, Daniela Drandi, Tina Bagratuni, Mary McMaster, Aldo M. Roccaro, Damien Roos-Weil, Merav Leiba, Yong Li, Luigi Qiu, Jian Hou, C. Fernandez De Larrea, Jorge J. Castillo, M. Dimopoulos, R. G. Owen, S. P. Treon, Z. R. Hunter
Summary: In addition to the MYD88L265P mutation, there is extensive information on the molecular mechanisms in Waldenstrom's Macroglobulinemia and its potential utility in the diagnosis and treatment tailoring. However, there are currently no consensus recommendations available. The key recommendations from the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) Consensus Panel 3 (CP3) focus on the necessity of molecular studies for proper diagnosis and monitoring.
SEMINARS IN HEMATOLOGY
(2023)
Letter
Oncology
Shayna Sarosiek, Steven P. Treon, Andrew R. Branagan, Jorge J. Castillo
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Bonnie W. Leung, Christopher J. Fay, Jordan T. Said, Anthony R. Sheets, Christine G. Lian, Jennifer R. Brown, Jorge J. Castillo, Shayna Sarosiek, Catherine Flynn, Nicole R. Leboeuf
LEUKEMIA & LYMPHOMA
(2023)
Correction
Oncology
Javier Munoz, Shayna Sarosiek, Jorge J. Castillo
Review
Pharmacology & Pharmacy
Shayna Sarosiek, Jorge J. Castillo
Summary: This review discusses the importance and effectiveness of current and emerging targeted therapies in the treatment of Waldenstrom macroglobulinemia (WM), highlighting the significant role of Bruton tyrosine kinase inhibitors. However, the specific adverse events and the indefinite duration of therapy should be carefully considered. Additionally, other novel targeted agents of interest are also introduced.
