Article
Oncology
Katherine Knorr, Jahan Rahman, Caroline Erickson, Eric Wang, Mara Monetti, Zhuoning Li, Juliana Ortiz-Pacheco, Andrew Jones, Sydney X. Lu, Robert F. Stanley, Maria Baez, Nina Fox, Cynthia Castro, Alessandra E. Marino, Caroline Jiang, Alex Penson, Simon J. Hogg, Xiaoli Mi, Hideaki Nakajima, Hiroyoshi Kunimoto, Koutarou Nishimura, Daichi Inoue, Benjamin Greenbaum, David Knorr, Jeffrey Ravetch, Omar Abdel-Wahab
Summary: Despite recent advances in AML treatment, targeting surface antigens in AML remains challenging due to shared expression across malignant and normal cells. This study identified unique expression of RNA helicase U5 snRNP200 on AML cells but not on normal hematopoietic precursors, as well as skewed Fc receptor distribution in the AML immune microenvironment. Anti-U5 snRNP200 antibodies engaging activating Fc receptors showed efficacy in AML models and were enhanced by combination with azacitidine.
Article
Hematology
Salvatore Perrone, Saveria Capria, Massimo Bernardi, Francesco Marchesi, Elettra Ortu La Barbera, Silvia Maria Trisolini, Clara Minotti, Mahnaz Shafii Bafti, Maria Cristina Scerpa, Antonino Mule, Fabio Ciceri, Maurizio Martelli, Giuseppe Cimino
Summary: Based on the retrospective analysis of patient data, it was found that approximately 55% of patients were able to successfully undergo hematopoietic stem cell transplantation (HSCT) after treatment with GO. However, the use of GO reduced the success rate of HSCT, indicating the need for further research on the impact of fractionated doses of GO on HSCT outcomes.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
John F. F. Marcelletti, Branimir I. I. Sikic
Summary: The purpose of this study was to evaluate the safety, tolerability, potential efficacy, and pharmacodynamics of Zos in combination with GO in elderly patients with RR AML. The results showed that the combination of Zos and GO achieved a significant ORR in elderly patients with RR AML, and the P-gp+ subgroup had a better OS.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Oncology
Upasana Sunil Arvindam, Paulien M. M. van Hauten, Dawn Schirm, Nicolaas Schaap, Willemijn Hobo, Bruce R. Blazar, Daniel A. Vallera, Harry Dolstra, Martin Felices, Jeffrey S. Miller
Summary: The development of a CLEC12A TriKE molecule targeting AML blasts and LSCs, which activates NK cells and drives NK cell priming while sparing healthy cells, highlights the potential clinical efficacy for the treatment of AML.
Review
Hematology
Brunangelo Falini, Lorenzo Brunetti, Maria Paola Martelli
Summary: Mutations of the nucleophosmin (NPM1) gene play a crucial role in adult acute myeloid leukemia (AML), with unique molecular, pathological, and clinical features. Accurate diagnosis and distinction of NPM1-mutated AML from other entities is important for guiding treatment decisions and assessing relapse risk. Monitoring measurable residual disease (MRD) using NPM1 mutations can provide valuable insights for therapeutic management after remission.
Article
Medicine, Research & Experimental
Lu Liu, Lin Yang, Xiaojun Liu, Menghan Liu, Jing Liu, Xuefeng Feng, Ziyuan Nie, Jianmin Luo
Summary: This study found that the expression of SEMA4D is increased in AML patients and is associated with risk stratification and prognosis. SEMA4D promotes the proliferation and inhibits apoptosis of AML cells by binding to its receptor, PlexinB1, and reduces the sensitivity of AML cells to daunorubicin. Furthermore, SEMA4D/PlexinB1 promotes the proliferation and survival of AML cells by activating the PI3K/Akt signaling pathway. The anti-SEMA4D antibody VX15/2503 can inhibit the proliferation of AML cells in xenograft mouse models, thereby inhibiting the development of AML.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Health Care Sciences & Services
Roberto Cairoli, Gianluca Furneri, Roberto Di Virgilio, Barbara Veggia, Felicetto Ferrara
Summary: Based on the ALFA-0701 study, gemtuzumab ozogamicin (GO) in combination with daunorubicin and cytarabine (DA) has been approved as the first line treatment for de novo acute-myeloid leukemia (AML). The cost-effectiveness of GO in combination with DA was assessed compared to DA alone, from the perspective of the Italian National Health Service.
BMC HEALTH SERVICES RESEARCH
(2023)
Article
Medicine, Research & Experimental
Sonia Jaramillo, Johannes Krisam, Lucian Le Cornet, Markus Kratzmann, Lukas Baumann, Tim Sauer, Martina Crysandt, Andreas Rank, Dirk Behringer, Lino Teichmann, Martin Goerner, Ralf-Ulrich Trappe, Christoph Roellig, Stefan Krause, Maher Hanoun, Olaf Hopfer, Gerhard Held, Sebastian Buske, Lars Fransecky, Sabine Kayser, Christoph Schliemann, Kerstin Schaefer-Eckart, Yousef Al-Fareh, Joerg Schubert, Thomas Geer, Martin Kaufmann, Arne Brecht, Dirk Niemann, Meinhard Kieser, Martin Bornhaeuser, Uwe Platzbecker, Hubert Serve, Claudia D. Baldus, Carsten Mueller-Tidow, Richard F. Schlenk
Summary: This randomized phase III trial aims to investigate the efficacy of adding gemtuzumab ozogamicin (GO) and glasdegib to the traditional treatment for older patients with acute myeloid leukemia (AML). A total of 252 evaluable patients will be needed to address the endpoints of measurable residual disease (MRD) and event-free survival (EFS) with a 2 by 2 factorial design. Ethical approval has been obtained and trial results will be disseminated through peer-reviewed journals and scientific conferences.
Article
Hematology
Raynier Devillier, Edouard Forcade, Alice Garnier, Sarah Guenounou, Sylvian Thepot, Gaelle Guillerm, Patrice Ceballos, Yosr Hicheri, Pierre-Yves Dumas, Pierre Peterlin, Mathilde Hunault-Berger, Marie-Christine Bene, Anne Bouvier, Patrice Chevallier, Didier Blaise, Norbert Vey, Arnaud Pigneux, Christian Recher, Anne Huynh
Summary: The study aimed to investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients aged > 60 years with acute myeloid leukemia (AML) in first complete remission (CR1). The results showed that allo-HSCT significantly improved relapse-free survival (RFS) and overall survival (OS) of these patients, indicating that allo-HSCT is the best curative option for fit older patients with AML.
Article
Oncology
Nicholas J. Short, Gautam Borthakur, Naveen Pemmaraju, Courtney D. Dinardo, Tapan M. Kadia, Elias Jabbour, Marina Konopleva, Walid Macaron, Jing Ning, Junsheng Ma, Sherry Pierce, Yesid Alvarado, Koji Sasaki, Koichi Takahashi, Zeev Estrov, Lucia Masarova, Ghayas C. Issa, Guillermo Montalban-Bravo, Michael Andreeff, Jan A. Burger, Darla Miller, Lynette Alexander, Aung Naing, Guillermo Garcia-Manero, Farhad Ravandi, Naval Daver
Summary: This study evaluates various immunotherapeutic agents and combinations in relapsed/refractory AML and shows that azacitidine + venetoclax + GO appears to be the most promising regimen. The study also demonstrates the feasibility of efficiently evaluating novel therapies through a multi-arm trial in AML.
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Raphael Itzykson, Elise Fournier, Celine Berthon, Christoph Rollig, Thorsten Braun, Alice Marceau-Renaut, Cecile Pautas, Olivier Nibourel, Emilie Lemasle, Jean-Baptiste Micol, Lionel Ades, Delphine Lebon, Jean-Valere Malfuson, Lauris Gastaud, Laure Goursaud, Emmanuel Raffoux, Kevin-James Wattebled, Philippe Rousselot, Xavier Thomas, Sylvain Chantepie, Thomas Cluzeau, Hubert Serve, Nicolas Boissel, Christine Terre, Karine Celli-Lebras, Claude Preudhomme, Christian Thiede, Herve Dombret, Claude Gardin, Nicolas Duployez
Summary: This study identified genetic mutations in AML patients that independently predict overall survival, providing a simple and robust prognostic model. By combining cytogenetic risk and mutations in specific genes, patients can be categorized into different prognostic tiers.
Article
Medicine, General & Internal
Rathnamitreyee Vegunta, Ronen Harel, Amir Steinberg
Summary: Chemotherapy remains the standard treatment for AML, but the optimal dose and safety profile when combined with new therapies like gemtuzumab-ozogamicin and FLT3 inhibitors are still being studied. Limited data suggest that intensified daunorubicin combined with gemtuzumab-ozogamicin may be effective for AML treatment, but may result in a significant decrease in platelet count.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Review
Oncology
Rabea Mecklenbrauck, Michael Heuser
Summary: The introduction of new targeted therapies to the treatment of acute myeloid leukemia (AML) offers new opportunities but also presents new challenges. This review summarizes the current knowledge on the main mechanisms of resistance to targeted therapies in AML, including FLT3 inhibitors, IDH inhibitors, gemtuzumab-ozogamicin, and venetoclax. Understanding these mechanisms can help develop strategies to overcome treatment resistance.
CLINICAL & EXPERIMENTAL METASTASIS
(2022)
Article
Oncology
Philip N. Moquist, Tim D. Bovee, Andrew B. Waight, Jamie A. Mitchell, Jamie B. Miyamoto, Marsha L. Mason, Kim K. Emmerton, Nicole Stevens, Cindy Balasubramanian, Jessica K. Simmons, Robert P. Lyon, Peter D. Senter, Svetlana O. Doronina
Summary: Auristatins are clinically validated anti-tubulin agents classified based on their membrane permeability and cytotoxic bystander activity on neighboring cells. Development of novel auristatins combines attributes of both categories, displaying both bystander activity and cytotoxicity on multidrug-resistant cell lines. Optimization of hydrophobicity and structure can lead to highly active free drugs and antibody-drug conjugates with in vivo bystander activities.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Oncology
Roberta Ranieri, Giulia Pianigiani, Sofia Sciabolacci, Vincenzo Maria Perriello, Andrea Marra, Valeria Cardinali, Sara Pierangeli, Francesca Milano, Ilaria Gionfriddo, Lorenzo Brunetti, Maria Paola Martelli, Brunangelo Falini
Summary: NPM1 mutations are the most common genetic alteration in AML, and NPM1-mutated AML is regarded as a distinct genetic entity. This study provides an overview of potential targeted therapies against NPM1-mutated AML, including strategies to interfere with oligomerization and abnormal traffic of NPM1, induce protein degradation, and target nucleolar structure integrity. Therapeutic results with BCL-2 inhibitor and menin inhibitors, as well as immunotherapeutic approaches, are also discussed.
Letter
Hematology
Elizabeth F. Krakow, Roland B. Walter, Julia M. Nathe, Tess Perez, Ali Ahmed, Nayak Polissar, Ljubomir Miljacic, Anna B. Halpern, Mary E. D. Flowers, Eli Estey
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Roland B. Walter
Summary: Despite the approval of new drugs, deaths from acute myeloid leukemia (AML) remain common. Radioimmunotherapy (RIT) targeting cell surface antigens with radiolabeled antibodies has emerged as an important research area to improve outcomes in AML.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Article
Oncology
George S. Laszlo, Johnnie J. Orozco, Allie R. Kehret, Margaret C. Lunn, Jenny Huo, Donald K. Hamlin, D. Scott Wilbur, Shannon L. Dexter, Melissa L. Comstock, Shyril O'Steen, Brenda M. Sandmaier, Damian J. Green, Roland B. Walter
Summary: This study developed At-211-based RIT targeting CD123, demonstrating potent and target-specific anti-leukemia efficacy in mouse models.
Article
Hematology
Corentin Orvain, Jacob A. Wilson, Min Fang, Brenda M. Sandmaier, Eduardo Rodriguez-Arboli, Brent L. Wood, Megan Othus, Frederick R. Appelbaum, Roland B. Walter
Summary: Measurable residual disease (MRD) before hematopoietic cell transplantation (HCT) is an independent prognostic factor for acute myeloid leukemia (AML) patients. The combination of residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry (MFC) improves risk assessment before HCT and provides complementary prognostic information for post-HCT outcomes in patients with cytogenetically abnormal AML undergoing allogeneic HCT.
Letter
Oncology
Megan Othus, Ian Thomas, Xu Wang, Cono Ariti, Priyanka Mehta, Mia Sydenham, Robert K. Hills, Alan K. Burnett, Sucha Nand, Sarit Assouline, Laura C. Michaelis, Harry P. Erba, Nigel Russell, Kathleen F. Kerr, Roland B. Walter, Mike Dennis
LEUKEMIA & LYMPHOMA
(2023)
Meeting Abstract
Hematology
Gabrielle Paras, Megan Othus, Carole M. Shaw, Katie Russell, Anna B. Halpern, Jacob S. Appelbaum, Paul C. Hendrie, Roland B. Walter, Mary-Elizabeth M. Percival
Meeting Abstract
Hematology
Noam E. Kopmar, Megan Othus, Olivia Gilbert, Kelda Schonhoff, Carole M. Shaw, Kathryn Russell, Anna B. Halpern, Jacob S. Appelbaum, Roland B. Walter, Paul C. Hendrie, Bart L. Scott, Mary-Elizabeth M. Percival
Article
Biophysics
Roland B. Walter, Brenda M. Sandmaier, Megan Othus, Corentin Orvain, Eduardo Rodriguez-Arboli, Masumi U. Oshima, Gary Schoch, Chris Davis, H. Joachim Deeg, Rainer Storb
Summary: Reduced intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning regimens are viable options for allogeneic hematopoietic cell transplantation (HCT) in AML patients. However, the relative efficacies and toxicities of these regimens are not well-defined. This study compared outcomes between RIC and NMA HCT patients and found no significant differences in relapse risk, relapse-free survival, overall survival, and non-relapse mortality. These findings suggest that the choice between RIC and NMA conditioning may not significantly impact outcomes in AML patients undergoing allografting.
BONE MARROW TRANSPLANTATION
(2023)
Article
Oncology
Gabrielle Paras, Megan Othus, Kelda Schonhoff, Carole Shaw, Mohamed Sorror, Anna B. Halpern, Jacob Appelbaum, Paul Hendrie, Roland B. Walter, Elihu H. Estey, Mary-Elizabeth M. Percival
Letter
Oncology
Sarit Assouline, Laura C. Michaelis, Megan Othus, Annette E. Hay, Roland B. Walter, Meagan A. Jacoby, Mark A. Schroeder, Geoffrey L. Uy, Lisa Y. Law, Faisal Cheema, Kendra L. Sweet, Adam S. Asch, Jijun (Jane) Liu, Anna B. Moseley, Tracy Maher, Laura L. Kingsbury, Min Fang, Jerald Radich, Richard F. Little, Harry P. Erba
LEUKEMIA & LYMPHOMA
(2023)
Article
Oncology
Corentin Orvain, Eduardo Rodriguez-Arboli, Megan Othus, Brenda M. Sandmaier, H. Joachim Deeg, Frederick R. Appelbaum, Roland B. Walter
Summary: This study retrospectively analyzed 739 patients with de novo AML, 125 with antecedent hematologic disorder (AHD)/AML, and 115 with therapy-related AML who received allografts while in first or second remission. The results showed that relative to patients with de novo AML, relapse rates were similar for patients with AHD and therapy-related AML after multivariable adjustment, as were relapse-free survival and overall survival. Non-relapse mortality was higher for AHD AML. These findings suggest that the clinical history by itself has limited prognostic value for AML patients undergoing allografting.
Editorial Material
Oncology
Raffaele Palmieri, Luca Maurillo, Maria Ilaria Del Principe, Giovangiacinto Paterno, Roland Bruno Walter, Adriano Venditti, Francesco Buccisano
Article
Oncology
Michelle Y. Y. Zhang, Megan Othus, Carole Shaw, Kelda G. G. Schonhoff, Anna B. B. Halpern, Jacob Appelbaum, Paul C. C. Hendrie, Roland B. B. Walter, Elihu H. H. Estey, Mary-Elizabeth M. Percival
Summary: Patients with acute myeloid leukemia (AML) who have previously received hypomethylating agents (HMA) have a poor prognosis. High intensity induction chemotherapy may improve outcomes in these patients.
LEUKEMIA & LYMPHOMA
(2023)
Letter
Oncology
Noam E. Kopmar, Ted Gooley, Niall Curley, Kathryn Russell, Carole Shaw, Kelda Schonhoff, John Lim, Anna B. Halpern, Roland B. Walter, Bart L. Scott, Jacob Appelbaum, Paul C. Hendrie, Elihu H. Estey, Mary-Elizabeth M. Percival
LEUKEMIA & LYMPHOMA
(2023)
Letter
Oncology
Lauren Shih, Megan Othus, Kelda Schonhoff, Carole Shaw, Jacob Appelbaum, Anna B. Halpern, Pamela S. Becker, Roland B. Walter, Elihu Estey, Mary-Elizabeth Percival