Article
Immunology
Joseph Sassine, Fareed Khawaja, Terri Lynn Shigle, Victoria Handy, Farnaz Foolad, Samuel L. Aitken, Ying Jiang, Richard Champlin, Elizabeth Shpall, Katy Rezvani, Ella J. Ariza-Heredia, Roy F. Chemaly
Summary: Primary prophylaxis with letermovir in CMV-seropositive allogeneic HCT recipients is associated with significant reductions in refractory or resistant CMV infections, nonrelapse mortality at week 48, as well as CS-CMVi and CMV end-organ disease. This approach effectively prevents difficult-to-treat CMV infections and improves outcomes after allogeneic HCT.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Marta Santos Bravo, Valentin Tilloy, Nicolas Plault, Sonsoles Sanchez Palomino, Maria Mar Mosquera, Mireia Navarro Gabriel, Francesc Fernandez Aviles, Maria Suarez Lledo, Montserrat Rovira, Asuncion Moreno, Laura Linares, Marta Bodro, Sebastien Hantz, Sophie Alain, Maria Angeles Marcos
Summary: We provide comprehensive data on the clinical correlates of both CMV genotypic follow-up by standard and deep sequencing and the clinical outcomes, as well as recombinant phenotypic results of this novel mutation. Our study emphasizes the importance of clinical follow-up in combination with genotypic and phenotypic studies for the assessment and optimization of patients experiencing HCMV relapses or not responding to antiviral therapy. This information may be important for other researchers and clinicians working in the field to improve the care of transplant patients since drug-resistant CMV infections are an important emerging problem even with the new antiviral development.
MICROBIOLOGY SPECTRUM
(2022)
Article
Immunology
Hannah N. Imlay, Daniel R. Kaul
Summary: Until recently, available drugs for CMV prevention and treatment in transplant patients have been limited by toxicity and resistance issues, with letermovir being the first new drug approved for CMV prevention since 2003. The efficacy of letermovir in treating established CMV infection or disease remains largely unstudied, while the investigational agent maribavir shows promise as a preemptive treatment option with unique mechanisms of action. Ongoing studies will define the efficacy of these drugs in patients with refractory or resistant CMV disease.
CLINICAL INFECTIOUS DISEASES
(2021)
Review
Virology
Carlos Solano, Estela Gimenez, Eliseo Albert, Jose L. Pinana, David Navarro
Summary: Letermovir has been approved by the US FDA for prophylaxis of CMV infection in adult allogeneic stem cell transplant recipients. Real-world experience has validated the clinical trial results, showing that it significantly reduces the risk of CMV infection and improves survival. However, further investigation is needed to address issues such as viral load threshold, impact on CMV-specific T-cell responses, and prevention of LMV-resistant strains.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Medicine, General & Internal
Ajit P. Limaye, Klemens Budde, Atul Humar, Flavio Vincenti, Dirk R. J. Kuypers, Robert P. Carroll, Nicole Stauffer, Yoshihiko Murata, Julie M. Strizki, Valerie L. Teal, Christopher L. Gilbert, Barbara A. Haber
Summary: This study compared the efficacy and safety of letermovir with valganciclovir in preventing cytomegalovirus (CMV) disease in kidney transplant recipients. Results showed that letermovir was as effective as valganciclovir in preventing CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Surgery
Tobias Veit, Dieter Munker, Juergen Barton, Katrin Milger, Teresa Kauke, Bruno Meiser, Sebastian Michel, Michael Zoller, Hans Nitschko, Oliver T. Keppler, Jurgen Behr, Nikolaus Kneidinger
Summary: This study assessed the therapeutic efficacy of letermovir in lung transplant recipients with difficult to treat CMV infections. Most patients responded rapidly to letermovir treatment, showing significant reduction in CMV viral load and clearance of infection. However, a small percentage of patients developed a mutation conferring resistance to letermovir.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Hematology
Joshua A. Hill, Danniel Zamora, Hu Xie, Laurel A. Thur, Colleen Delaney, Ann Dahlberg, Steven A. Pergam, Wendy M. Leisenring, Michael Boeckh, Filippo Milano
Summary: Letermovir is effective in preventing clinically significant CMV infection after CBT, but there is a higher incidence of delayed-onset infections after discontinuation, requiring close monitoring and consideration for extended prophylaxis.
Article
Infectious Diseases
Angela Chiereghin, Tamara Belotti, Eva Caterina Borgatti, Nicola Fraccascia, Giulia Piccirilli, Maura Fois, Michele Borghi, Gabriele Turello, Liliana Gabrielli, Riccardo Masetti, Arcangelo Prete, Stefano Fanti, Tiziana Lazzarotto
Summary: This case report demonstrates the off-label use of letermovir as preemptive antiviral therapy in a pediatric patient with drug-resistant CMV infection, showing good tolerability and effectiveness in suppression of viral replication.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Oncology
Massimo Martino, Annalisa Pitino, Mercedes Gori, Benedetto Bruno, Alessandra Crescimanno, Vincenzo Federico, Alessandra Picardi, Stefania Tringali, Claudia Ingrosso, Paola Carluccio, Domenico Pastore, Gerardo Musuraca, Annalisa Paviglianiti, Adriana Vacca, Bianca Serio, Gabriella Storti, Nicola Mordini, Salvatore Leotta, Michele Cimminiello, Lucia Prezioso, Barbara Loteta, Anna Ferreri, Fabrizia Colasante, Emanuela Merla, Luisa Giaccone, Alessandro Busca, Maurizio Musso, Renato Scalone, Nicola Di Renzo, Serena Marotta, Patrizio Mazza, Pellegrino Musto, Immacolata Attolico, Carmine Selleri, Filippo Antonio Canale, Marta Pugliese, Giovanni Tripepi, Gaetana Porto, Giovanni Martinelli, Angelo Michele Carella, Claudio Cerchione
Summary: This study evaluated the effectiveness and safety of letermovir for CMV prophylaxis in a real-world setting, showing significant reduction in clinically important CMV infections and diseases.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Susan E. Prockop, Aisha Hasan, Ekaterina Doubrovina, Parastoo B. Dahi, Irene Rodriguez-Sanchez, Michael Curry, Audrey Mauguen, Genovefa A. Papanicolaou, Yiqi Su, JinJuan Yao, Maria Arcila, Farid Boulad, Hugo Castro-Malaspina, Christina Cho, Kevin J. Curran, Sergio Giralt, Nancy A. Kernan, Guenther Koehne, Ann Jakubowski, Esperanza Papadopoulos, Miguel-Angel Perales, Ioannis Politikos, Keith Price, Annamalai Selvakumar, Craig S. Sauter, Roni Tamari, Teresa Vizconde, James W. Young, Richard J. O'Reilly
Summary: The adoptive transfer of CMVpp65-sensitized T cells from a third-party donor can improve the prognosis for recipients of hematopoietic stem cell transplant with refractory CMV viremia and disease, providing potential new treatments for these patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Hematology
Danniel Zamora, Elizabeth R. Duke, Hu Xie, Bradley C. Edmison, Brenda Akoto, Richard Kiener, Terry Stevens-Ayers, Ralf Wagner, Marco Mielcarek, Wendy M. Leisenring, Keith R. Jerome, Joshua T. Schiffer, Greg Finak, Stephen C. De Rosa, Michael Boeckh
Summary: The study suggests that letermovir may delay CMV-specific cellular reconstitution, possibly due to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality can help identify patients at risk for late CMV infection after HCT.
Article
Hematology
Ian Pang, Peggy Chen, Gertrude V. Trinh, Mats Remberger, Igor Novitzky-Basso, Armin Gerbitz, Dennis D. Kim, Rajat Kumar, Wilson Lam, Arjun D. Law, Jeffrey H. Lipton, Auro Viswabandya, Ivan Pasic, Jonas Mattsson, Fotios V. Michelis
Summary: Letermovir prophylaxis starting at day +21 post-alloHCT reduces CMV reactivation, with no impact on posttransplant outcomes.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Review
Medicine, Research & Experimental
Jennifer L. Saullo, Rachel A. Miller
Summary: Cytomegalovirus (CMV) is a common viral pathogen in the transplant population and selecting the best preventive strategy depends on various factors. Letermovir (LTV) is a novel CMV therapy that inhibits viral DNA synthesis and lacks side effects and resistance mechanisms. LTV is approved for CMV prevention in adult hematopoietic cell transplant recipients and is being increasingly used off-label. This review summarizes important concepts of CMV management, focusing on LTV pharmacology, clinical experience, and future prospects.
ANNUAL REVIEW OF MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Sunwen Chou, Steven Kleiboeker
Summary: Genotypic testing for letermovir resistance revealed multiple sequence variants, with codon 325 mutations being the most common and capable of causing high-level resistance. Additionally, new mutations were identified, some of which conferred a 2-to 5-fold increase in the drug's inhibitory concentrations. These findings highlight the ongoing concern of the emergence of absolute letermovir resistance during therapy.
ANTIVIRAL RESEARCH
(2022)
Article
Microbiology
Lena Royston, Stavroula Masouridi-Levrat, Verena Gotta, Eva Royston, Caroline Pressacco-Brossier, Yasmine Abi Aad, David Tonoli, Abderrahim Karmime, Murielle Jayo, Christian Van Delden, Pierre Lescuyer, Marc Pfister, Yves Chalandon, Dionysios Neofytos
Summary: This study evaluated the efficacy and safety of letermovir, an anti-cytomegalovirus drug, in hematopoietic stem cell transplant recipients. The results showed that the blood concentration of letermovir remained stable during treatment, but had no noticeable associations with clinical efficacy. The study also found potential associations between concomitantly administered drugs and adverse events, highlighting the need for further research.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Public, Environmental & Occupational Health
Sarah E. Simmons, Ricardo Carrion, Kendra J. Alfson, Hilary M. Staples, Chetan Jinadatha, William R. Jarvis, Priya Sampathkumar, Roy F. Chemaly, Fareed Khawaja, Mark Povroznik, Stephanie Jackson, Keith S. Kaye, Robert M. Rodriguez, Mark A. Stibich
Summary: The study found that the pulsed-xenon ultraviolet disinfection system significantly reduced the load of SARS-CoV-2 on hard surfaces and N95 respirators, effectively lowering the risk of infection.
INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
(2021)
Article
Immunology
Joseph Sassine, Fareed Khawaja, Terri Lynn Shigle, Victoria Handy, Farnaz Foolad, Samuel L. Aitken, Ying Jiang, Richard Champlin, Elizabeth Shpall, Katy Rezvani, Ella J. Ariza-Heredia, Roy F. Chemaly
Summary: Primary prophylaxis with letermovir in CMV-seropositive allogeneic HCT recipients is associated with significant reductions in refractory or resistant CMV infections, nonrelapse mortality at week 48, as well as CS-CMVi and CMV end-organ disease. This approach effectively prevents difficult-to-treat CMV infections and improves outcomes after allogeneic HCT.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Georgios Angelidakis, Fareed Khawaja, Victor E. Mulanovich, Natalie Dailey-Garnes, Ella Ariza-Heredia, Roy F. Chemaly
Summary: This study reports on two hematopoietic cell transplant recipients with severe influenza infections who were treated with a combination of baloxavir and oseltamivir. The study discusses possible reasons for their different responses.
MICROBES AND INFECTION
(2022)
Editorial Material
Biophysics
Fareed Khawaja, Roy F. Chemaly
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
Ajay Sheshadri, Alberto A. Goizueta, Vickie R. Shannon, David London, Guillermo Garcia-Manero, Hagop M. Kantarjian, Farhad Ravandi-Kashani, Tapan M. Kadia, Marina Y. Konopleva, Courtney D. DiNardo, Sherry Pierce, Abdulrazzak Zarifa, Aya A. Albittar, Linda L. Zhong, Fechukwu O. Akhmedzhanov, Muhammad H. Arain, Mansour Alfayez, Ahmad Alotaibi, Mehmet Altan, Aung Naing, Tito R. Mendoza, Myrna C. B. Godoy, Girish Shroff, Sang T. Kim, Saadia A. Faiz, Dimitrios P. Kontoyiannis, Fareed Khawaja, Kristofer Jennings, Naval G. Daver
Summary: This study found a high incidence of pneumonia in AML patients treated with ICI therapy, and pneumonia significantly increased mortality. Older age and baseline shortness of breath increased the risk of pneumonia, while female sex and higher baseline platelet counts decreased the risk of pneumonia.
Article
Public, Environmental & Occupational Health
Fareed Khawaja, Krithika Srinivasan, Amy Spallone, Adina Feldman, Sherry Cantu, Ella Ariza-Heredia, Tanya Dvordak, Amin Alousi, Sairah Ahmed, Marina George, Elizabeth Frenzel, Micah Bhatti, Roy F. Chemaly
Summary: This article describes the early experience with nosocomial respiratory viral infections (RVIs) at a cancer center in the first year of the pandemic. The investigation revealed that nosocomial transmission of COVID-19 most likely occurred from employees to patients. The severity of viral infections led to enhancement of infection control measures, and the impact of COVID-19 vaccination on infection control policies requires further study.
AMERICAN JOURNAL OF INFECTION CONTROL
(2023)
Meeting Abstract
Hematology
Rishab Prakash, James Long, Paul Edelkamp, Mark Knafl, Sairah Ahmed, Fareed Khawaja, Loretta J. Nastoupil, Joanna-Grace Manzano, Victor Mulanovich, Sabitha Prabhakaran, Andrew Futreal, Scott E. Woodman, Swaminathan Padmanabhan Iyer
Article
Respiratory System
Christopher D. Bertini Jr, Fareed Khawaja, Ajay Sheshadri
Summary: COVID-19 often leads to more severe infections in immunocompromised patients, especially those with hematologic malignancies, SOT recipients, and patients with ARD, resulting in higher hospitalization, disease severity, and mortality rates. Treatment approaches for these patients are similar to immunocompetent individuals, but lack high-quality data. Vaccinations are recommended but less effective in immunocompromised patients. It is crucial for the medical and scientific communities to focus on the vulnerability of immunocompromised patients during the ongoing pandemic. Research focusing on this population will provide valuable insights into mitigating harms in these high-risk individuals.
CLINICS IN CHEST MEDICINE
(2023)
Letter
Gastroenterology & Hepatology
Chia-Yu Chiu, Krina Patel, Sheeba K. Thomas, Fareed Khawaja, Natalie J. M. Dailey Garnes, Hans C. Lee, Maro Ohanian, Ying Jiang, Lan S. Wang, Jessica P. Hwang, Harrys A. Torres
HEPATOLOGY INTERNATIONAL
(2023)
Article
Biology
Hiba Dagher, Anne-Marie Chaftari, Ishwaria M. Subbiah, Alexandre E. Malek, Ying Jiang, Peter Lamie, Bruno Granwehr, Teny John, Eduardo Yepez, Jovan Borjan, Cielito Reyes-Gibby, Mary Flores, Fareed Khawaja, Mala Pande, Noman Ali, Raniv Rojo, Daniel D. Karp, Patrick Chaftari, Ray Hachem, Issam I. Raad
Summary: This study aims to assess the post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery. The study found that over half of cancer patients continue to experience long-term COVID-19 symptoms after recovery, with the most common symptoms being fatigue, sleep disturbances, myalgias, and gastrointestinal symptoms. Most of the patients were managed on an outpatient basis, with only 8.5% requiring readmission for COVID-19-related reasons.
Article
Biology
Issam I. Raad, Ray Hachem, Nigo Masayuki, Tarcila Datoguia, Hiba Dagher, Ying Jiang, Vivek Subbiah, Bilal Siddiqui, Arnaud Bayle, Robert Somer, Ana Fernandez Cruz, Edward Gorak, Arvinder Bhinder, Nobuyoshi Mori, Nelson Hamerschlak, Samuel Shelanski, Tomislav Dragovich, Yee Elise Vong Kiat, Suha Fakhreddine, Abi Hanna Pierre, Roy F. Chemaly, Victor Mulanovich, Javier Adachi, Jovan Borjan, Fareed Khawaja, Bruno Granwehr, Teny John, Eduardo Yepez Yepez, Harrys A. Torres, Natraj Reddy Ammakkanavar, Marcel Yibirin, Cielito C. Reyes-Gibby, Mala Pande, Noman Ali, Raniv Dawey Rojo, Shahnoor M. Ali, Rita E. Deeba, Patrick Chaftari, Takahiro Matsuo, Kazuhiro Ishikawa, Ryo Hasegawa, Ramon Aguado-Noya, Alvaro Garcia Garcia, Cristina Traseira Puchol, Dong Gun Lee, Monica Slavin, Benjamin Teh, Cesar A. Arias, Dimitrios P. Kontoyiannis, Alexandre E. Malek, Anne-Marie Chaftari
Summary: This international multicenter study aimed to identify independent risk factors for increased 30-day mortality in COVID-19 patients with and without cancer. The study analyzed data from 16 international centers and found that cancer itself was not an independent risk factor for increased mortality. Older age and lymphopenia were the main predictors of 30-day mortality in all patients, and remdesivir was the only therapeutic agent associated with decreased mortality.
Article
Oncology
Chia-Yu Chiu, Sairah Ahmed, Sheeba K. Thomas, Lan Sun Wang, Khalis Mustafayev, Luis E. Fayad, William G. Wierda, Fareed Khawaja, Harrys A. Torres
Summary: A retrospective analysis found that HBV reactivation occurred in 3 out of 29 patients receiving BTK inhibitors, indicating the need for monitoring in this scenario. The risk of HBV reactivation is intermediate in patients with past HBV infection who receive BTK inhibitors. Universal anti-HBV prophylaxis is not recommended, but monitoring for HBV reactivation is warranted in patients with past HBV infection receiving BTK inhibitors.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Mehmet Altan, Felipe Soto, Linda L. Zhong, Fechukwu O. Akhmedzhanov, Nathaniel R. Wilson, Abdulrazzak Zarifa, Aya A. Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J. Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L. Gibbons, Ara A. Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A. Faiz, Vickie R. Shannon, Girish Shroff, Myrna C. B. Godoy, Naval G. Daver, Saumil Gandhi, Tito R. Mendoza, Aung Naing, Carrie Daniel-MacDougall, John Heymach, Ajay Sheshadri
Summary: This study retrospectively analyzed 419 patients with advanced non-small cell lung cancer who received immune checkpoint inhibitor therapy and found a high incidence of pneumonitis, which significantly increased the risk of death. The risk of pneumonitis was higher in patients without a smoking history and patients with interstitial lung disease.
Article
Oncology
Fareed Khawaja, Marilyne Daher, Amy Spallone, Roy F. Chemaly
Summary: COVID-19 disproportionately affects cancer patients due to their weakened immune systems. Vaccination is a strategy to mitigate the impact, offering some level of protection against severe complications like respiratory failure and death, with limited safety concerns. This review discusses available COVID-19 vaccines, their efficacy and safety in cancer patients, current vaccination guidelines, and future directions.
Article
Hematology
Fareed Khawaja, Genovefa Papanicolaou, Sanjeet Dadwal, Steven A. Pergam, John R. Wingard, Zeinab El Boghdadly, Maheen Z. Abidi, Alpana Waghmare, Zainab Shahid, Laura Michaels, Joshua A. Hill, Mini Kamboj, Michael Boeckh, Jeffery J. Auletta, Roy F. Chemaly
Summary: COVID-19 disproportionately affects immunocompromised and elderly patients. Hematopoietic cell transplantation and CAR T-cell recipients may have suboptimal immune response to COVID-19 vaccines. Guidelines for optimizing vaccine use in these patients are provided by professional societies.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
