Article
Oncology
Alice S. Mims
Summary: For newly diagnosed AML patients, treatment strategies depend on disease subtype and genetic mutations. While most patients with TP53 mutations do not respond well to current therapies, the emergence of targeted agents like venetoclax and glasdegib provides new options for those ineligible for intensive induction regimens.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)
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
Oncology
Kelly J. Norsworthy, Xin Gao, Chia-Wen Ko, E. Dianne Pulte, Jiaxi Zhou, Yutao Gong, Yuan Li Shen, Jonathon Vallejo, Thomas E. Gwise, Rajeshwari Sridhara, Albert B. Deisseroth, Ann T. Farrell, R. Angelo de Claro, Gideon M. Blumenthal, Richard Pazdur
Summary: The study explores the associations between response and survival outcomes in newly diagnosed acute myeloid leukemia (AML) patients undergoing intensive chemotherapy. The analysis reveals a moderate association between complete remission (CR) rate and overall survival (OS), and a strong association between event-free survival (EFS) and OS. However, the confidence intervals are wide, and the results became moderate when using alternative definitions for EFS. Patient-level analysis shows that CR responders have better OS compared to CRi or CRp responders and nonresponders.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
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
Oncology
Joshua F. Zeidner, Daniel J. Lee, Mark Frattini, Gil D. Fine, Judy Costas, Kathryn Kolibaba, Stephen P. Anthony, David Bearss, B. Douglas Smith
Summary: Alvocidib, when combined with 7+3 induction therapy, shows promising clinical activity in newly diagnosed acute myeloid leukemia patients, indicating the potential for further investigation of Alvocidib combinations in this population.
CLINICAL CANCER RESEARCH
(2021)
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
Hematology
Nicholas J. Short, Hagop Kantarjian
Summary: Outcomes of older patients with acute myeloid leukaemia are usually worse due to aggressive disease biology and poorer tolerance of chemotherapy, but low-intensity venetoclax-based therapy has shown improved results in these patients.
LANCET HAEMATOLOGY
(2022)
Article
Oncology
Colin D. Godwin, Eduardo Rodriguez-Arboli, Megan Othus, Anna B. Halpern, Jacob S. Appelbaum, Mary-Elizabeth M. Percival, Paul C. Hendrie, Vivian G. Oehler, Sioban B. Keel, Janis L. Abkowitz, Jason P. Cooper, Ryan D. Cassaday, Elihu H. Estey, Roland B. Walter
Summary: Gemtuzumab ozogamicin (GO) improves outcomes when combined with intensive chemotherapy for acute myeloid leukemia (AML). This study found that a fractionated dosing schedule of GO (GO3) can be safely combined with other chemotherapy drugs and leads to superior outcomes in favorable-risk AML patients compared to chemotherapy alone.
Editorial Material
Hematology
Gary Schiller
Summary: The study introduces a convenient clinical prognostic tool based on cytogenetic and molecular profiling to identify which group of older and fit AML patients may benefit from intensive induction and consolidation chemotherapy.
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
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
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
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
Oncology
Francesco Mannelli, Paola Guglielmelli, Paola Fazi, Enrico Crea, Alfonso Piciocchi, Marco Vignetti, Sergio Amadori, Fabrizio Pane, Adriano Venditti, Alessandro M. Vannucchi
Summary: The evolution into a blast phase is a fatal event in myeloproliferative neoplasms, with a median survival of 3-6 months. Clinical trials with innovative approaches are needed for this category of patients. The ENABLE trial aims to test the combination of venetoclax and decitabine in patients with post-MPN blast phase, who have a poor prognosis.
Article
Oncology
Roberto Mina, Pellegrino Musto, Delia Rota-Scalabrini, Laura Paris, Barbara Gamberi, Angelo Palmas, Sara Aquino, Paolo de Fabritiis, Nicola Giuliani, Luca De Rosa, Alessandro Gozzetti, Claudia Cellini, Luca Bertamini, Andrea Capra, Daniela Oddolo, Iolanda Donatella Vincelli, Sonia Ronconi, Vincenzo Pavone, Norbert Pescosta, Michele Cea, Francesca Fioritoni, Stelvio Ballanti, Mariella Grasso, Elena Zamagni, Angelo Belotti, Mario Boccadoro, Francesca Gay
Summary: Maintenance treatment with carfilzomib plus lenalidomide for two years prolongs progression-free survival in patients with multiple myeloma. However, patients with two or more high-risk cytogenetic abnormalities still have an increased risk of progression and death.
Editorial Material
Oncology
Raffaele Palmieri, Luca Maurillo, Maria Ilaria Del Principe, Giovangiacinto Paterno, Roland Bruno Walter, Adriano Venditti, Francesco Buccisano
Article
Hematology
Luca Guarnera, Gentiana Elena Trotta, Valentina Boldrini, Lucia Cardillo, Ilaria Cerroni, Valeria Mezzanotte, Gianmario Pasqualone, Arianna Savi, Beatrice Borsellino, Elisa Buzzatti, Raffaele Palmieri, Giovangiacinto Paterno, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Maria Ilaria Del Principe
Summary: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined.
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
(2023)
Article
Oncology
Gianfranco Catalano, Alessandra Zaza, Cristina Banella, Elvira Pelosi, Germana Castelli, Elisabetta de Marinis, Ariela Smigliani, Serena Travaglini, Tiziana Ottone, Mariadomenica Divona, Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Emanuele Ammatuna, Ugo Testa, Clara Nervi, Adriano Venditti, Maria Teresa Voso, Nelida Ines Noguera
Summary: We characterized the metabolic background in different types of Acute Myeloid Leukemia (AML) by comparing the metabolism of primary AML blasts with that of normal hematopoietic progenitors. The AML blasts showed lower respiratory and glycolytic capacities compared to hematopoietic precursors. AML blasts can be grouped based on Proton Leak values, and the group with high Proton Leak and high respiratory capacity had shorter overall survival time and overexpression of MCL1 protein. MCL1 was found to directly bind to HK2 on the outer mitochondrial membrane, suggesting its role in inducing glycolysis and promoting resistance to therapy in AML cells.
Article
Oncology
L. Maurillo, A. Spagnoli, A. Candoni, C. Papayannidis, E. Borlenghi, D. Lazzarotto, L. Fianchi, M. Sciume, M. E. Zannier, F. Buccisano, M. I. Del Principe, V. Mancini, M. Breccia, R. Fanin, E. Todisco, M. Lunghi, R. Palmieri, N. Fracchiolla, P. Musto, G. Rossi, A. Venditti
Summary: This study compared the efficacy of azacitidine and decitabine in elderly patients with untreated AML. The results showed similar outcomes in terms of complete remission, overall survival, and disease free survival between the two groups.
Letter
Medicine, General & Internal
Luca Guarnera, Elisa Buzzatti, Francesco Marchesi, Daniele Armiento, Carla Mazzone, Saveria Capria, Emilia Scalzulli, Francesco Malfona, Sabina Chiaretti, Raffaele Palmieri, Giovangiacinto Paterno, Chiara Franzese, Fabrizio Bonanni, Arianna Savi, Gianmario Pasqualone, Federico Moretti, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Maria Ilaria Del Principe
Article
Oncology
Silvia Calabria, Giulia Ronconi, Letizia Dondi, Carlo Piccinni, Antonella Pedrini, Immacolata Esposito, Alice Addesi, Giuseppe Rossi, Felicetto Ferrara, Adriano Venditti, Nello Martini
Summary: This study aimed to identify newly diagnosed patients with acute myeloid leukemia in 2017 in Italy, and assess their probability of receiving allogeneic stem cell transplantation and survival. From the Italian National Health Service database, adults with in-hospital diagnosis of acute myeloid leukemia in 2017 were selected. Results showed that only patients treated with intensive chemotherapy underwent allogeneic stem cell transplantation and had higher survival rates.
Review
Hematology
Adriano Venditti, Roberto Cairoli, Morena Caira, Paola Finsinger, Fabio Finocchiaro, Benedetta Neri, Daniela De Benedittis, Giuseppe Rossi, Felicetto Ferrara
Summary: Age alone is no longer the sole indicator to determine eligibility for intensive chemotherapy in patients with acute myeloid leukemia (AML). The evaluation of comorbidities and overall performance status is also important in tailoring therapeutic options. Consensus criteria have been proposed to define eligibility for intensive and nonintensive chemotherapy in AML patients, and assessment of fitness is now essential in selecting the most appropriate treatment.
EXPERT REVIEW OF HEMATOLOGY
(2023)
Article
Oncology
T. Ottone, G. Silvestrini, R. Piazza, S. Travaglini, C. Gurnari, F. Marchesi, A. M. Nardozza, E. Fabiani, E. Attardi, L. Guarnera, M. Divona, P. Ricci, M. A. Irno Consalvo, S. Ienzi, R. Arcese, A. Biagi, L. Fiori, M. Novello, A. Mauriello, A. Venditti, L. Anemona, M. T. Voso
Summary: By analyzing the transcriptome profile of AML patients, researchers found that TWIST1, ECM-receptor interaction, and focal-adhesion pathways were significantly deregulated. The study also showed that metformin can interfere with these processes.
Review
Oncology
Anna Aureli, Beatrice Marziani, Adriano Venditti, Tommaso Sconocchia, Giuseppe Sconocchia
Summary: The emergence of targeted therapies has revolutionized the management of B-lineage acute lymphoblastic leukemia, allowing for optimism in replacing traditional treatments. However, few patients currently benefit from these therapies, necessitating further research to improve outcomes, particularly in patients resistant to current treatments. This review discusses new therapeutic options, including bispecific antibodies, antibody-drug conjugates, and CAR-based therapies.
Review
Oncology
Maria Christina Cox, Fabiana Esposito, Massimiliano Postorino, Adriano Venditti, Arianna Di Napoli
Summary: This systematic review explores the clinical impact of serum paraprotein (PP) in low- and high-grade mature B-cell malignancies. The analysis shows that serum PP is consistently associated with high-risk biological and clinical features, as well as poor outcome. Screening for serum PP should be included in the diagnostic work-up of all mature B-cell malignancies.
Letter
Health Care Sciences & Services
Mario Luppi, Elena Bandieri, Adriano Venditti, Paolo Corradini
BMJ SUPPORTIVE & PALLIATIVE CARE
(2023)
Article
Hematology
Jorge Sierra, Pau Montesinos, Xavier Thomas, Laimonas Griskevicius, Thomas Cluzeau, Denis Caillot, Ollivier Legrand, Clara Minotti, Mario Luppi, Firas Farkas, Bourras-Rezki Bengoudifa, Geralyn Gilotti, Sejla Hodzic, Alessandro Rambaldi, Adriano Venditti
Summary: The pivotal RATIFY study demonstrated that midostaurin combined with standard chemotherapy significantly reduced mortality in adult patients with newly diagnosed FLT3(mut) acute myeloid leukemia. This open-label, multicenter phase 3b trial aimed to further assess the safety and efficacy of midostaurin plus chemotherapy in different age groups. The results showed that the safety and efficacy of midostaurin remained consistent with previous findings regardless of age, sex, or induction regimen.
Article
Hematology
Michael Luebbert, Pierre W. Wijermans, Michal Kicinski, Sylvain Chantepie, Walter J. F. M. Van der Velden, Richard Noppeney, Laimonas Griskevicius, Andreas Neubauer, Martina Crysandt, Radovan Vrhovac, Mario Luppi, Stephan Fuhrmann, Ernesta Audisio, Anna Candoni, Olivier Legrand, Robin Foa, Gianluca Gaidano, Danielle van Lammeren-Venema, Eduardus F. M. Posthuma, Mels Hoogendoorn, Anne Giraut, Marian Stevens-Kroef, Joop H. Jansen, Aniek O. de Graaf, Fabio Efficace, Emanuele Ammatuna, Jean-Pierre Vilque, Ralph Waesch, Heiko Becker, Nicole Blijlevens, Ulrich Duehrsen, Frederic Baron, Stefan Suciu, Sergio Amadori, Adriano Venditti, Gerwin Huls
Summary: This study compares the efficacy and safety of decitabine monotherapy with intensive chemotherapy in older patients with acute myeloid leukemia. The results show that 10-day decitabine monotherapy is as effective and safer than 3 + 7 chemotherapy in older patients.
LANCET HAEMATOLOGY
(2023)