Review
Pharmacology & Pharmacy
Uri Greenbaum, Partow Kebriaei, Samer A. Srour, Amanda Olson, Qaiser Bashir, Sattva S. Neelapu, Katayoun Rezvani, Elizabeth J. Shpall
Summary: Cancer immunotherapy has made significant progress recently with CAR T cells showing promising results in treating malignancies, yet also presenting new immune-mediated adverse events and toxicities. The main toxicities associated with CAR T cell therapy include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Oncology
Jinrong Yang, Weilin Zhou, Dan Li, Ting Niu, Wei Wang
Summary: This article summarizes the application and research progress of BCMA-targeting CAR T cell therapy in the treatment of multiple myeloma, as well as measures to improve efficacy and safety.
Review
Critical Care Medicine
Shin Yeu Ong, John H. Baird
Summary: Chimeric antigen receptor (CAR) T-cell therapy is an innovative treatment approach that has shown remarkable efficacy against several hematologic malignancies. However, it can lead to unique and sometimes severe toxicities, requiring intensive care unit admission. Intensivists play a crucial role in managing the immune-mediated toxicities and adverse events associated with CAR T-cell therapy.
JOURNAL OF INTENSIVE CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Christopher Schorr, Jorge Forindez, Manuel Espinoza-Gutarra, Rakesh Mehta, Natalie Grover, Fabiana Perna
Summary: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B-cell hematological malignancies, but it is associated with various toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), and thrombotic events. A retrospective study on 140 adult patients who received CAR T-cell therapy revealed a thrombosis incidence of 7.14%, primarily involving venous events and occurring around 23.5 days post-infusion. D-Dimer elevation and ICANS grade were significantly associated with post-CAR T-cell therapy thrombosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Zixun Yin, Ya Zhang, Xin Wang
Summary: B-cell non-Hodgkin lymphoma is a heterogeneous disease that remains incurable, necessitating the development of novel therapies. CAR-T cell therapy shows promising potential in refractory or relapsed B-NHL, but comes with adverse effects. New antigen-targeted CAR-T products and four-generation CAR-T are rapidly developing to overcome these limitations.
BIOMARKER RESEARCH
(2021)
Article
Hematology
Paolo Strati, Sairah Ahmed, Fateeha Furqan, Luis E. Fayad, Hun J. Lee, Swaminathan P. Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria A. Rodriguez, Felipe Samaniego, Raphael E. Steiner, Michael Wang, Chelsea C. Pinnix, Sandra B. Horowitz, Lei Feng, Ryan Sun, Catherine M. Claussen, Misha C. Hawkins, Nicole A. Johnson, Prachee Singh, Haleigh Mistry, Swapna Johncy, Sherry Adkins, Partow Kebriaei, Elizabeth J. Shpall, Michael R. Green, Christopher R. Flowers, Jason Westin, Sattva S. Neelapu
Summary: For patients with relapsed or refractory large B-cell lymphoma undergoing CAR T-cell therapy, the use of corticosteroids for toxicity management may impact clinical outcomes. Higher cumulative dose, prolonged duration, and early initiation of corticosteroids were associated with shorter progression-free and overall survival.
Review
Engineering, Biomedical
Huanqing Niu, Penghui Zhao, Wujin Sun
Summary: CAR-T cells have achieved breakthrough efficacies against hematological malignancies, but their unsatisfactory efficacies in solid tumors limit their applications. Biomaterial engineering provides promising strategies to improve CAR-T cell therapies, including the engineering of gene delivery nanoparticles for CAR transduction and the development of nano-/microparticles or implantable scaffolds for local delivery or stimulation of CAR-T cells. These biomaterial-based strategies can potentially reduce the cost of CAR-T cell manufacturing and enhance their efficacy in solid tumors.
ACTA BIOMATERIALIA
(2023)
Article
Biochemistry & Molecular Biology
Sophia Stock, Anna-Kristina Kluever, Stefan Endres, Sebastian Kobold
Summary: Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in treating specific hematological malignancies. However, many patients do not respond or relapse after treatment. Strategies such as combining CAR T cells with other treatments and using clinically approved compounds have been investigated to improve this therapy.
Review
Pharmacology & Pharmacy
Taewoong Choi, Yubin Kang
Summary: Although treatment outcomes for multiple myeloma patients have greatly improved in the past two decades, the disease remains incurable. New immunotherapies, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, have emerged to treat multiple myeloma. This article provides a comprehensive review of the clinical efficacy, safety, and potential resistance mechanisms of current myeloma CAR-T therapies, with a focus on B Cell Maturation Antigen (BCMA) as the most successful target. The article also discusses novel strategies to enhance the effectiveness of myeloma CAR-T therapy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Immunology
Christina Kazzi, Valeriya Kuznetsova, Pakeeran Siriratnam, Sarah Griffith, Shu Wong, Constantine S. Tam, Rubina Alpitsis, Andrew Spencer, Terence J. O'Brien, Charles B. Malpas, Mastura Monif
Summary: This systematic review aimed to characterize the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy. The study found that cognition outcomes varied at different time points, with some patients experiencing stable, improved, or reduced cognition. Cognitive symptoms were most common in the acute stage after infusion, and most deficits resolved within one to two weeks. However, some patients continued to experience persistent deficits in the subacute and chronic stages.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Multidisciplinary Sciences
Mohadeseh Mirzaee Godarzee, Bashdar Mahmud Hussen, Ehsan Razmara, Benyamin Hakak-Zargar, Fatemeh Mohajerani, Hamed Dabiri, Mohammed Fatih Rasul, Mohammad Hossein Ghazimoradi, Sadegh Babashah, Majid Sadeghizadeh
Summary: Chimeric antigen receptor (CAR) therapy is a genetic engineering approach that enhances the ability of immune cells to detect and eliminate tumor cells expressing new antigens on their surfaces. However, its application is limited by various side effects. Improving design and using combined receptors can enhance the performance of CAR T cells. This review discusses the limitations and risk factors associated with CAR T cell therapy and explores alternative approaches for developing the next generation of CAR T cells.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Oncology
Wenwen Wei, Dong Yang, Xi Chen, Dandan Liang, Liqun Zou, Xudong Zhao
Summary: This review summarizes the characteristics of non-B-cell acute leukemia and the efficacy and challenges of CAR-T cell therapy in treating this type of leukemia.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biophysics
Katerina Nezvalova-Henriksen, Claudia Langebrake, Tiene Bauters, Maria-Estela Moreno-Martinez, Emelie Ahnfelt, Heidi Ekelund, Vera Domingos, Vera Pires, Agnes Bonnin, Ines Bojanic, Yolanda Cabrerizo, Sofie Terwel, Alice Tam
Summary: CAR-T cells are a type of gene therapy that enables T cells to recognize and destroy cancer cells. They are currently licensed to treat certain blood cancers and are used in both children and adults. Hospital pharmacies play a crucial role in ensuring appropriate governance, handling, suitability, and pharmacovigilance.
BONE MARROW TRANSPLANTATION
(2023)
Article
Oncology
Hui Zhang, Pengfei Wang, Zhuoyan Li, Yingyi He, Wenting Gan, Hua Jiang
Summary: The study tested the safety and efficacy of anti-CLL1 CAR T-cell therapy in pediatric patients with R/R-AML, showing promising results with a high rate of complete remission and minimal residual disease negativity in patients. The therapy was well tolerated with low-grade and manageable adverse events, indicating the potential of autologous anti-CLL1 CAR T-cell therapy as a safe and efficient treatment option for children with R/R-AML. Further investigation is warranted to explore its full potential.
CLINICAL CANCER RESEARCH
(2021)
Review
Cardiac & Cardiovascular Systems
Massimiliano Camilli, Luca Maggio, Lorenzo Tinti, Priscilla Lamendola, Gaetano Antonio Lanza, Filippo Crea, Antonella Lombardo
Summary: CAR-T cell therapies are innovative treatments for advanced and refractory onco-hematological malignancies. However, these therapies can lead to a range of adverse events, including cardiovascular toxicities. The pathophysiological basis of cardiotoxicity related to CAR-T cells is still being investigated, but inflammation seems to play a crucial role. Understanding the mechanisms and risk factors will help identify patients who need close cardiological monitoring and long-term follow-up. This review aims to highlight CAR-T cell-related cardiovascular complications and provide insight into surveillance strategies and cardiotoxicity management protocols.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Editorial Material
Hematology
Bhagirathbhai Dholaria, Ashwin Kishtagari, Emily F. Mason
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Letter
Biophysics
Carlyn Rose Tan, Noel Estrada-Merly, Heather Landau, Lazaros Lekakis, Rahul Banerjee, Hira Mian, Saad Z. Usmani, Amr Hanbali, Hillard M. Lazarus, Robert A. Kyle, Bhagirathbhai Dholaria, Susan Bal, Christopher Strouse, Hemant S. Murthy, Baldeep Wirk, Taiga Nishihori, Shaji Kumar, Nina Shah, Muzaffar Qazilbash, Anita D'Souza
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
Luciano J. Costa, Saurabh Chhabra, Eva Medvedova, Bhagirathbhai R. Dholaria, Timothy M. Schmidt, Kelly N. Godby, Rebecca Silbermann, Binod Dhaka, Susan Bal, Smith Gid, Anita D'Souza, Aric Hall, Pamela Hardwick, James Omel, Robert F. Cornell, Parameswaran Had, Natalie S. Callander
Summary: Dara-KRd, AHCT, and MRD response-adapted consolidation lead to a high rate of MRD negativity in NDMM patients. This strategy creates the opportunity of MRD surveillance as an alternative to indefinite maintenance for patients with 0 or 1 HRCA.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Siddharth Kunte, Lisa Rybicki, Auro Viswabandya, Roni Tamari, Asad Bashey, Alla Keyzner, Madiha Iqbal, Michael R. Grunwald, Bhagirathbhai Dholaria, Hany Elmariah, Michael Ozga, Anurag Singh, Sameem Abedin, Amy E. DeZern, Richard J. Jones, Vikas Gupta, Aaron T. Gerds, Tania Jain
Summary: The study demonstrates that haplo-BMT with PTCy is effective in treating myelofibrosis, but splenomegaly >= 22 cm and bone marrow grafts are associated with an increased risk of relapse.
Article
Oncology
Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie Jose Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, Patrick M. Reagan
Summary: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown durable long-term responses with manageable safety in patients with relapsed/refractory mantle cell lymphoma (MCL) and may benefit those with high-risk characteristics.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Michael Boyiadzis, Mei-Jie Zhang, Karen Chen, Hisham Abdel-Azim, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M. Badawy, Minoo Battiwalla, Nelli Bejanyan, Vijaya Raj Bhatt, Valerie Brown, Paul Castillo, Jan Cerny, Edward A. Copelan, Charles Craddock, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, Christen L. Ebens, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Madiha Iqbal, Omer Jamy, Mohamed A. Kharfan-Dabaja, Nandita Khera, Hillard M. Lazarus, Richard Lin, Dipenkumar Modi, Sunita Nathan, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, Akshay Sharma, Melhem Solh, John L. Wagner, Trent Wang, Kirsten M. Williams, Lena E. Winestone, Baldeep Wirk, Christopher S. Hourigan, Mark Litzow, Partow Kebriaei, Marcos de Lima, Kristin Page, Daniel J. Weisdorf
Summary: We investigated the impact of the number of induction/consolidation cycles on the outcomes of adult AML patients who received allo-HCT between 2008 and 2019. Our findings suggest that the number of induction cycles to complete remission (CR) has an impact on overall survival (OS) in patients who received myeloablative conditioning, with better OS observed in patients who achieved CR after 1 cycle compared to those who required 2 cycles or more. In contrast, the number of induction cycles did not affect OS in patients who received reduced-intensity conditioning. Consolidation therapy prior to allo-HCT was associated with improved OS in patients who achieved CR after 1 cycle. The presence of detectable minimal residual disease (MRD) at the time of allo-HCT did not impact outcomes in myeloablative allo-HCT, but was associated with an increased risk of relapse in reduced-intensity allo-HCT. Allo-HCT in patients with primary induction failure had significantly worse OS compared to allo-HCT in patients who achieved CR after 1-3 cycles.
Article
Oncology
Kedar Kirtane, Maija Reblin, Laura B. Oswald, Nathaly Irizarry-Arroyo, Rachael McCormick, Frederick L. Locke, Dana Ketcher
Summary: This article describes the psychosocial characteristics of patients undergoing cellular immunotherapies and their caregivers, including patient/caregiver distress, coping, and caregiver burden and preparedness.
LEUKEMIA & LYMPHOMA
(2023)
Article
Oncology
Jason R. Westin, Frederick L. Locke, Michael Dickinson, Armin Ghobadi, Mahmoud Elsawy, Tom van Meerten, David B. Miklos, Matthew L. Ulrickson, Miguel-Angel Perales, Umar Farooq, Luciano Wannesson, Lori Leslie, Marie Jose Kersten, Caron A. Jacobson, John M. Pagel, Gerald Wulf, Patrick Johnston, Aaron P. Rapoport, Linqiu Du, Saran Vardhanabhuti, Simone Filosto, Jina Shah, Julia T. Snider, Paul Cheng, Christina To, Olalekan O. Oluwole, Anna Sureda
Summary: This study reported the outcomes of a preplanned subgroup analysis of patients aged >= 65 years with relapsed/refractory large B-cell lymphoma in the ZUMA-7 trial. The results showed that axicabtagene ciloleucel as a second-line therapy can improve event-free survival and have a manageable safety profile and improved patient-reported outcomes.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Yucai Wang, Preetesh Jain, Frederick L. Locke, Matthew J. Maurer, Matthew J. Frank, Javier L. Munoz, Saurabh Dahiya, Amer M. Beitinjaneh, Miriam T. Jacobs, Joseph P. Mcguirk, Julie M. Vose, Andre Goy, Charalambos Andreadis, Brian T. Hill, Kathleen A. Dorritie, Olalekan O. Oluwole, Abhinav Deol, Jonas Paludo, Bijal Shah, Trent Wang, Rahul Banerjee, David B. Miklos, Aaron P. Rapoport, Lazaros Lekakis, Armin Ghobadi, Sattva S. Neelapu, Yi Lin, Michael L. Wang, Michael D. Jain
Summary: This study evaluated the efficacy and toxicity of Brexucabtagene autoleucel (brexu-cel) for relapsed/refractory mantle cell lymphoma (MCL) in the standard-of-care setting. The results showed that the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Erin A. Dean, Gregory J. Kimmel, Matthew J. Frank, Ali Bukhari, Nasheed M. Hossain, Michael D. Jain, Saurabh Dahiya, David B. Miklos, Philipp M. Altrock, Frederick L. Locke
Summary: We investigated the relationship between total metabolic tumor volume (MTV) on positron emission tomography (PET) scans and circulating tumor DNA (ctDNA) in patients with relapsed/refractory large B-cell lymphoma receiving axicabtagene ciloleucel (axi-cel). Our results suggested that nonprogressing hypermetabolic lesions on 1-month PET represent ongoing treatment responses, and their composition may be elucidated by concurrently examining the ctDNA.
Meeting Abstract
Oncology
K. M. Kortuem, N. Bahlis, M. -V. Mateos, K. Weisel, B. Dholaria, A. Garfall, H. Goldschmidt, T. Martin, D. Morillo, D. Reece, D. Hurd, P. Rodriguez-Otero, M. Bhutani, A. D'Souza, A. Oriol, E. Askari, J. San-Miguel, N. van de Donk, D. Vishwamitra, Wang S. X. Lin, T. Prior, L. Vandenberk, Damiette M. -A. Smit, J. Goldberg, R. Waesch, A. Chari
ONCOLOGY RESEARCH AND TREATMENT
(2022)
Meeting Abstract
Oncology
Paula Rodriguez-Otero, Anita D'Souza, Donna Ellen Reece, Niels W. C. J. van de Donk, Ajai Chari, Amrita Y. Krishnan, Thomas G. Martin, Maria-Victoria Mateos, Daniel Morillo, David Duane Hurd, Laura Rosinol, Anna Sureda Balari, Ralph Wasch, Deeksha Vishwamitra, Shun Xin Wang Lin, Thomas Prior, Lien Vandenberk, Marie-Anne Damiette Smit, Albert Oriol Rocafiguera, Bhagirathbhai R. Dholaria
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Hematology
Ameet Patel, Karina Wilkerson, Heidi Chen, Deva Sharma, Michael Byrne, Jennifer Green, Salyka Sengsayadeth, Bhagirathbhai Dholaria, Bipin Savani, Wichai Chinratanalab, Reena Jayani, Katie Gatwood, Brian G. Engelhardt, Carrie Kitko, James Connelly, Adetola Kassim
Summary: This study evaluated the occurrence of recurrent thrombotic events in patients with sickle cell disease (SCD) who underwent allo-HCT. The results showed a significant reduction in the prevalence of venous thromboembolic (VTE) events and ischemic cerebrovascular accidents (CVAs) after allo-HCT. Compared to the control group, patients who underwent allo-HCT were less likely to develop recurrent thrombotic events.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Hemant S. Murthy, Kwang Woo Ahn, Noel Estrada-Merly, Hassan B. Alkhateeb, Susan Bal, Mohamed A. Kharfan-Dabaja, Bhagirathbhai Dholaria, Francine Foss, Lohith Gowda, Deepa Jagadeesh, Craig Sauter, Muhammad Bilal Abid, Mahmoud Aljurf, Farrukh T. Awan, Ulrike Bacher, Sherif M. Badawy, Minoo Battiwalla, Chris Bredeson, Jan Cerny, Saurabh Chhabra, Abhinav Deol, Miguel Angel Diaz, Nosha Farhadfar, Cesar Freytes, James Gajewski, Manish J. Gandhi, Siddhartha Ganguly, Michael R. Grunwald, Joerg Halter, Shahrukh Hashmi, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Antonio Martin Jimenez-Jimenez, Matt Kalaycio, Rammurti Kamble, Maxwell M. Krem, Hillard M. Lazarus, Aleksandr Lazaryan, Joseph Maakaron, Pashna N. Munshi, Reinhold Munker, Aziz Nazha, Taiga Nishihori, Olalekan O. Oluwole, Guillermo Orti, Dorothy C. Pan, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Nakhle S. Saba, Bipin Savani, Sachiko Seo, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, John L. Wagner, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber
Summary: This study analyzed the outcomes of alloHCT in 266 patients with T-PLL and aimed to identify predictors of post-transplantation relapse and survival. The results showed that reduced-intensity conditioning alloHCT was associated with long-term disease-free survival.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
V. Patel, B. Dholaria, R. V. Jayani, S. Sengsayadeth, M. Wigger, S. Horst, J. Lindenfeld, K. Schlendorf, H. Ooi, M. Brinkley, S. Zalawadiya, D. Pedrotty, J. Hoffman, R. Hung, S. Goodman, B. Savani, A. Kassim, S. Harrell, L. Punnoose.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)