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365 results on '"Aaron T. Gerds"'

1. Interferons in the treatment of myeloproliferative neoplasms

Author

Pankit Vachhani, John Mascarenhas, Prithviraj Bose, Gabriela Hobbs, Abdulraheem Yacoub, Jeanne M. Palmer, Aaron T. Gerds, Lucia Masarova, Andrew T. Kuykendall, Raajit K. Rampal, Ruben Mesa, and Srdan Verstovsek

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

Published
2024
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2. Momelotinib in Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials

Author

Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Aaron T. Gerds, Vikas Gupta, Srdan Verstovsek, Miklos Egyed, Uwe Platzbecker, Jiří Mayer, Sebastian Grosicki, Árpád Illés, Tomasz Woźny, Stephen T. Oh, Donal McLornan, Ilya Kirgner, Sung-Soo Yoon, Claire N. Harrison, Barbara Klencke, Mei Huang, Jun Kawashima, and Ruben Mesa

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts

Published
2023
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3. The ABNL-MARRO 001 study: a phase 1–2 study of randomly allocated active myeloid target compound combinations in MDS/MPN overlap syndromes

Author

Tamara K. Moyo, Jason H. Mendler, Raphael Itzykson, Ashwin Kishtagari, Eric Solary, Adam C. Seegmiller, Aaron T. Gerds, Gregory D. Ayers, Amy E. Dezern, Aziz Nazha, Peter Valent, Arjan A. van de Loosdrecht, Francesco Onida, Lisa Pleyer, Blanca Xicoy Cirici, Raoul Tibes, Klaus Geissler, Rami S. Komrokji, Jing Zhang, Ulrich Germing, David P. Steensma, Daniel H. Wiseman, Michael Pfeilstöecker, Chiara Elena, Nicholas C. P. Cross, Jean-Jacques Kiladjian, Michael Luebbert, Ruben A. Mesa, Guillermo Montalban-Bravo, Guillermo F. Sanz, Uwe Platzbecker, Mrinal M. Patnaik, Eric Padron, Valeria Santini, Pierre Fenaux, Michael R. Savona, and On Behalf of the MDS/MPN International Working Group

Subjects
ABNL MARRO, MDS/MPN, ASTX727, Itacitinib, Phase 1b/2, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) comprise several rare hematologic malignancies with shared concomitant dysplastic and proliferative clinicopathologic features of bone marrow failure and propensity of acute leukemic transformation, and have significant impact on patient quality of life. The only approved disease-modifying therapies for any of the MDS/MPN are DNA methyltransferase inhibitors (DNMTi) for patients with dysplastic CMML, and still, outcomes are generally poor, making this an important area of unmet clinical need. Due to both the rarity and the heterogeneous nature of MDS/MPN, they have been challenging to study in dedicated prospective studies. Thus, refining first-line treatment strategies has been difficult, and optimal salvage treatments following DNMTi failure have also not been rigorously studied. ABNL-MARRO (A Basket study of Novel therapy for untreated MDS/MPN and Relapsed/Refractory Overlap Syndromes) is an international cooperation that leverages the expertise of the MDS/MPN International Working Group (IWG) and provides the framework for collaborative studies to advance treatment of MDS/MPN and to explore clinical and pathologic markers of disease severity, prognosis, and treatment response. Methods ABNL MARRO 001 (AM-001) is an open label, randomly allocated phase 1/2 study that will test novel treatment combinations in MDS/MPNs, beginning with the novel targeted agent itacitinib, a selective JAK1 inhibitor, combined with ASTX727, a fixed dose oral combination of the DNMTi decitabine and the cytidine deaminase inhibitor cedazuridine to improve decitabine bioavailability. Discussion Beyond the primary objectives of the study to evaluate the safety and efficacy of novel treatment combinations in MDS/MPN, the study will (i) Establish the ABNL MARRO infrastructure for future prospective studies, (ii) Forge innovative scientific research that will improve our understanding of pathogenetic mechanisms of disease, and (iii) Inform the clinical application of diagnostic criteria, risk stratification and prognostication tools, as well as response assessments in this heterogeneous patient population. Trial registration This trial was registered with ClinicalTrials.gov on August 19, 2019 (Registration No. NCT04061421).

Published
2022
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4. S167: EFFICACY AND SAFETY OF LUSPATERCEPT FOR THE TREATMENT OF ANEMIA IN PATIENTS WITH MYELOFIBROSIS: RESULTS FROM THE ACE-536-MF-001 STUDY

Author

Aaron T. Gerds, Claire Harrison, Jean-Jacques Kiladjian, Ruben Mesa, Alessandro Vannucchi, Rami S. Komrokji, Prithviraj Bose, Marina Kremyanskaya, Adam Mead, Jason Gotlib, Fabian Sanabria, Niloufar Marsousi, Ana Carolina Giuseppi, Huijing Jiang, Jeanne Palmer, Kelly Mccaul, Vincent Ribrag, Srdan Verstovsek, and Francesco Passamonti

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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5. S210: AN OPEN-LABEL, GLOBAL, PHASE (PH) 1B/2 STUDY ADDING NAVTEMADLIN (NVTM) TO RUXOLITINIB (RUX) IN PATIENTS (PTS) WITH PRIMARY OR SECONDARY MYELOFIBROSIS (MF) WHO HAVE A SUBOPTIMAL RESPONSE TO RUX

Author

John Mascarenhas, Tania Jain, Salman Otoukesh, Aaron T. Gerds, Alessandro Lucchesi, Iberia Romina Sosa, Kamel Laribi, Elena Mishchenko, Atanas Radinoff, Giulia Benevolo, Alessandro M. Vannucchi, Francoise Boyer, Philippe Quittet, Markus Radsak, Antoine Machet, Prithviraj Bose, Zhuying Huang, Hope Qamoos, Jesse Mcgreivy, Wayne P. Rothbaum, Srdan Verstovsek, and Francesco Passamonti

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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8. P1030: SPLEEN VOLUME REDUCTION PREDICTS SURVIVAL IN MYELOFIBROSIS PATIENTS ON PACRITINIB BUT NOT BEST AVAILABLE THERAPY: PERSIST-2 LANDMARK OVERALL SURVIVAL ANALYSIS

Author

Jan Bewersdorf, Helen Ajufo, Claire Harrison, Francesca Palandri, John Mascarenhas, Jeanne Palmer, Aaron T. Gerds, Jean-Jacques Kiladjian, Andrii Derkach, Karisse Roman-Torres, Sarah Buckley, and Raajit K Rampal

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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9. Clinical outcomes of patients with myelofibrosis after immediate transition to momelotinib from ruxolitinib

Author

Ruben Mesa, Srdan Verstovsek, Uwe Platzbecker, Vikas Gupta, David Lavie, Pilar Giraldo, Christian Recher, Jean-Jacques Kiladjian, Stephen T. Oh, Aaron T. Gerds, Timothy Devos, Francesco Passamonti, Alessandro M. Vannucchi, Miklos Egyed, Ewa Lech-Maranda, Andrzej Pluta, Lars Nilsson, Kazuya Shimoda, Donal McLornan, Jun Kawashima, Barbara Klencke, Mei Huang, Bryan Strouse, and Claire Harrison

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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12. Breath analysis in gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation

Author

Betty K. Hamilton, Lisa A. Rybicki, David Grove, Christina Ferraro, Jamie Starn, Brittany Hodgeman, Jamie Elberson, Victoria Winslow, Donna Corrigan, Aaron T. Gerds, Rabi Hanna, Matt E. Kalaycio, Ronald M. Sobecks, Navneet S. Majhail, and Raed A. Dweik

Subjects
Specialties of internal medicine, RC581-951
Abstract

Volatile organic compounds (VOCs) are generated during pathologic processes, and their assessment can be used to diagnose and monitor a variety of diseases. Given the role of the microbiome in graft-versus-host disease (GVHD), we hypothesized that microorganisms producing volatile metabolites may alter VOCs expelled in breath in patients with gastrointestinal (GI) GVHD. In this pilot study, exhaled breath samples were obtained from 19 patients with grade 2 to 4 acute GI GVHD, 10 patients with no GVHD at day 100, and 10 healthy control subjects; the samples were analyzed by using mass spectrometry. Overall, nine (47%) patients had grade 2 GVHD, eight (42%) patients had grade 3 GVHD, and two (11%) patients had grade 4 GVHD; 26% had upper GI, 21% had lower GI, and 53% had both upper and lower GI manifestations. Stepwise canonical discriminant analysis identified 5 VOCs distinguishing patients with and without GI GVHD: 2-propanol, acetaldehyde, dimethyl sulfide, isoprene, and 1-decene (Wilks' Λ, 0.43; F statistic, 6.08; P = .001). The model correctly classified 89% (17 of 19) and 90% (9 of 10) of patients with and without GI GVHD, respectively. Breath analysis is a feasible and promising noninvasive method to detect acute GI GVHD. Further study of serial breath analysis and the gut microbiome in a larger cohort are ongoing to validate these findings.

Published
2019
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13. Genomics of therapy-related myeloid neoplasms

Author

Teodora Kuzmanovic, Bhumika J. Patel, Srinivasa R. Sanikommu, Yasunobu Nagata, Hassan Awada, Cassandra M. Kerr, Bartlomiej P. Przychodzen, Babal K. Jha, Devendra Hiwase, Deepak Singhal, Anjali S. Advani, Aziz Nazha, Aaron T. Gerds, Hetty E. Carraway, Mikkael A. Sekeres, Sudipto Mukherjee, Jaroslaw P. Maciejewski, and Tomas Radivoyevitch

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2020
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16. An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm patients with AML

Author

Mohamed L. Sorror, Ted A. Gooley, Barry E. Storer, Aaron T. Gerds, Mikkael A. Sekeres, Bruno C. Medeiros, Eunice S. Wang, Paul J. Shami, Kehinde Adekola, Selina Luger, Maria R. Baer, David A. Rizzieri, Tanya M. Wildes, Jamie Koprivnikar, Julie Smith, Mitchell Garrison, Kiarash Kojouri, Tammy A. Schuler, Wendy M. Leisenring, Lynn E. Onstad, Pamela S. Becker, Jeannine S. McCune, Stephanie J. Lee, Brenda M. Sandmaier, Frederick R. Appelbaum, and Elihu H. Estey

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Abstract

We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients’ overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

Published
2023

17. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

Author

C.E. Geyer, J.E. Garber, R.D. Gelber, G. Yothers, M. Taboada, L. Ross, P. Rastogi, K. Cui, A. Arahmani, G. Aktan, A.C. Armstrong, M. Arnedos, J. Balmaña, J. Bergh, J. Bliss, S. Delaloge, S.M. Domchek, A. Eisen, F. Elsafy, L.E. Fein, A. Fielding, J.M. Ford, S. Friedman, K.A. Gelmon, L. Gianni, M. Gnant, S.J. Hollingsworth, S.-A. Im, A. Jager, Ó. Þ Jóhannsson, S.R. Lakhani, W. Janni, B. Linderholm, T.-W. Liu, N. Loman, L. Korde, S. Loibl, P.C. Lucas, F. Marmé, E. Martinez de Dueñas, R. McConnell, K.-A. Phillips, M. Piccart, G. Rossi, R. Schmutzler, E. Senkus, Z. Shao, P. Sharma, C.F. Singer, T. Španić, E. Stickeler, M. Toi, T.A. Traina, G. Viale, G. Zoppoli, Y.H. Park, R. Yerushalmi, H. Yang, D. Pang, K.H. Jung, A. Mailliez, Z. Fan, I. Tennevet, J. Zhang, T. Nagy, G.S. Sonke, Q. Sun, M. Parton, M.A. Colleoni, M. Schmidt, A.M. Brufsky, W. Razaq, B. Kaufman, D. Cameron, C. Campbell, A.N.J. Tutt, Paul Sevelda, Ferdinand Haslbauer, Monika Penzinger, Leopold Öhler, Christoph Tinchon, Richard Greil, Sonja Heibl, Rupert Bartsch, Viktor Wette, Christian F. Singer, Claudia Pasterk, Ruth Helfgott, Gunda Pristauz-Telsnigg, Herbert Stöger, Angsar Weltermann, Daniel Egle, Irene Thiel, David Fuchs, Holger Rumpold, Kathrin Strasser-Weippl, Beate Rautenberg, Volkmar Müller, Marcus Schmidt, Stefan Paepke, Mustafa Aydogdu, Christoph Thomssen, Joachim Rom, Christine Mau, Peter Fasching, Uwe-Jochen Göhring, Thorsten Kühn, Stefanie Noeding, Sherko Kümmel, John Hackmann, Elmar Stickeler, Abhishek Joshi, Joanna Dewar, Michael Friedlander, Kelly-Anne Phillips, Yoland Antill, Natasha Woodward, Ehtesham Abdi, Susan Tiley, Mathew George, David Boadle, Annabel Goodwin, Andre van der Westhuizen, George Kannourakis, Nicholas Murray, Nicole McCarthy, Judith Kroep, Maaike de Boer, Joan Heijns, Agnes Jager, Franciscus Erdkamp, Sandra Bakker, Gabe S. Sonke, Amer Sami, John Mackey, Catherine Prady, Andrea Eisen, Christine Desbiens, Erica Patocskai, Cristiano Ferrario, Karen Gelmon, Louise Bordeleau, Haji Chalchal, Saroj Niraula, null ido wolf, Elżbieta Senkus, François Duhoux, null Randal d’Hondt, Sylvie Luce, Daphné t’Kint de Roodenbeke, Konstantinos Papadimitriou, Marleen Borms, Claire Quaghebeur, William Jacot, Etienne Brain, Laurence Venat-Bouvet, Alain Lortholary, Zbigniew Nowecki, Fátima Cardoso, Richard Hayward, Santiago Bella, Mauricio Fernández Lazzaro, Norma Pilnik, Luis E. Fein, Cesar Blajman, Guillermo Lerzo, Mirta Varela, Juan Jose Zarba, Diego Kaen, Maria Victoria Constanzo, Joke Tio, Wulf Siggelkow, Christian Jackisch, Eva Maria Grischke, Dirk Zahm, Sara Tato-Varela, Sabine Schmatloch, Peter Klare, Andrea Stefek, Kerstin Rhiem, Oliver Hoffmann, Mustafa Deryal, Isolde Gröll, Peter Ledwon, Christoph Uleer, Petra Krabisch, Jochem Potenberg, Maren Darsow, Tjoung-Won Park-Simon, Heinz-Gert Höffkes, Till-Oliver Emde, Gerd Graffunder, Oliver Tomé, Dirk Forstmeyer, Jürgen Terhaag, Christoph Salat, Karin Kast, Steffi Weniger, Carsten Schreiber, Bernhard Heinrich, Max Dieterich, Michaela Penelope Wüllner, Raquel Andrés Conejero, José Ángel García Sáenz, Lourdes Calvo Martinez, Angels Arcusa Lanza, Serafín Morales Murillo, Fernando Henao Carrasco, Salvador Blanch Tormo, Isabel Álvarez López, Juan Ignacio Delgado Mingorance, Elena Álvarez Gomez, Marta Santisteban, Josefina Cruz Jurado, Vanesa Quiroga, Manuel Ruiz Borrego, Eduardo Martínez de Dueñas, Jose Enrique Alés Martínez, Juan De la Haba, Noelia Martínez Jañez, Álvaro Rodríguez Lescure, Antonio Antón Torres, Gema Llort Crusades, Santiago González-Santiago, Antonia Marquez Aragones, Ana Laura Ortega, Agusti Barnadas Molins, José Ignacio Chacón López-Muñiz, Miguel Martín Jiménez, Ana Santaballa Bertrán, César Rodríguez, Lucía González Cortijo, Elisabetta Cretella, Laura Cortesi, Enzo Maria Ruggeri, Claudio Verusio, Stefania Gori, Andrea Bonetti, Anna Maria Mosconi, Oskar Johannsson, Guy Jerusalem, Patrick Neven, Tünde Nagy, Graziella Pinotti, Marco A. Colleoni, Antonio Bernardo, Lorenzo Gianni, Eraldo Bucci, Laura Biganzoli, Konstantin Dedes, Urban Novak, Khalil Zaman, Jeremy Braybrooke, Matthew Winter, Daniel Rea, Muireann Kelleher, Sophie Barrett, Stephen Chan, Tamas Hickish, Jane Hurwitz, John Conibear, Apurna Jegannathen, Marina Parton, Andrew Tutt, Rozenn Allerton, Annabel Borley, Anne Armstrong, Ellen Copson, Nicola Levitt, Jean Abraham, Timothy Perren, Rebecca Roylance, Kazushige Ishida, Tatsuya Toyama, Norikazu Masuda, Junichiro Watanabe, Eriko Tokunaga, Takayuki Kinoshita, Yoshiaki Rai, Masahiro Takada, Yasuhiro Yanagita, Rikiya Nakamura, Takahiro Nakayama, Yasuto Naoi, Hiroji Iwata, Seigo Nakamura, Masato Takahashi, Kenjiro Aogi, Koichiro Tsugawa, Hirofumi Mukai, Toshimi Takano, Akihiko Osaki, Nobuaki Sato, Hideko Yamauchi, Yutaka Tokuda, Mitsuya Ito, Takeki Sugimoto, Shakeela W. Bahadur, Patricia A. Ganz, Min J. Lu, Monica M. Mita, James Waisman, Jonathan A. Polikoff, Melinda L. Telli, Samantha A. Seaward, J. Marie Suga, Lara N. Durna, Jennifer Fu Carney, Alex Menter, Ajithkumar Puthillath, Nitin Rohatgi, James H. Feusner, Kristie A. Bobolis, Peter D. Eisenberg, Derrick Wong, Virginia F. Borges, Alexander T. Urquhart, Erin W. Hofstatter, Edward C. McCarron, Claudine Isaacs, Pia Herbolsheimer, Ramya Varadarajan, Adam Raben, Ruby Anne E. Deveras, Frances Valdes-Albini, Reshma L. Mahtani, Jane L. Meisel, Bradley T. Sumrall, Cheryl F. Jones, Samuel N. Ofori, Kenneth N.M. Sumida, Mark Karwal, Deborah W. Wilbur, (Joe) Singh, David M. Spector, John Schallenkamp, Douglas E. Merkel, Shelly S. Lo, Pam G. Khosla, Massimo Cristofanilli, Lisa Flaum, Kent F. Hoskins, Melody A. Cobleigh, Elyse A. Lambiase, Olwen M. Hahn, Ira A. Oliff, Bryan A. Faller, James L. Wade, Nafisa D. Burhani, Amaryllis Gil, Harvey E. Einhorn, Anna M.V. Storniolo, Brian K. Chang, Maitri Kalra, Erwin L. Robin, Bilal Ansari, Priyanka Sharma, Shaker R. Dakhil, Richard L. Deming, John T. Cole, David S. Hanson, Augusto C. Ochoa, Judy E. Garber, Harvey Zimbler, Deborah K. Armstrong, Katherine H.R. Tkaczuk, David A. Riseberg, Brian M. O'Connor, Thomas H. Openshaw, Dana Zakalik, Cynthia M. Vakhariya, Anne F. Schott, Michael S. Simon, Thomas J. Doyle, Tareq Al Baghdadi, Amy VanderWoude, Patrick J. Flynn, Richard T. Zera, Bret E.B. Friday, Kathryn J. Ruddy, Ron Smith, null Ademuyiwa, Foluso Olabisi, Robert Ellis, Jay W. Carlson, null Marchello, Benjamin T, Edward A. Levine, Paul K. Marcom, Cameron B. Harkness, Antoinette R. Tan, William J. Charles, Charles S. Kuzma, Shonda Asaad, James E. Radford, Preston D. Steen, Madhu Unnikrishnan, Grant R. Seeger, Kirsten M.H. Leu, Mehmet S. Copur, Ralph J. Hauke, Gamini S. Soori, Bradley A. Arrick, Jennifer G. Reeder, Deborah L. Toppmeyer, Zoneddy R. Dayao, Sylvia Adams, Eleni Andreopoulou, Magnuson Allison, Jesus D. Anampa Mesias, Ruby Sharma, Bhuvaneswari Ramaswamy, Aaron T. Gerds, Robert R. Shenk, Howard M. Gross, Shruti Trehan, Wajeeha Razaq, Abdul H. Mansoor, Christie J. Hilton, Adam M. Brufsky, Chanh Huynh, Nabila Chowdhury, Susan M. Domchek, Elin R. Sigurdson, Terrence P. Cescon, Marc A. Rovito, Albert S. DeNittis, Victor G. Vogel, Thomas B. Julian, L.E. Boyle, Luis Baez-Diaz, Frank J. Brescia, John E. Doster, Robert D. Siegel, Lucas Wong, Tejal Patel, Julie R. Nangia, Catherine A. Jones, George M. Cannon, Harry D. Bear, Hetal Vachhani, Mary Wilkinson, Marie E. Wood, Fengting Yan, Xingwei Sui, Carol M. van Haelst, Jennifer M. Specht, Ying Zhuo, Rubina Qamar, Matthew L. Ryan, Abigail Stockham, Shamsuddin Virani, Arlene A. Gayle, Steven J. Jubelirer, Sobha Kurian, Mohamad A. Salkeni, Niklas Loman, Barbro Linderholm, Gustav Silander, Anna-Lotta Hallbeck, Anna von Wachenfeldt Väppling, Elsa Curtit, Catarina Cardoso, Sofia Braga, Miguel Abreu, Mafalda Casa-Nova, Mónica Nave, Eva María Ciruelos Gil, Judith Balmaña Gelpi, Adela Fernández Ortega, Josep Gumà Padró, Begoña Bermejo de las Heras, María González Cao, Juan Cueva Bañuelos, Jesús Alarcon Company, Gemma Viñas Villaró, Laura García Estevez, Jens Huober, Steffi Busch, Tanja Fehm, Antje Hahn, Andrea Grafe, Thomas Noesselt, Thomas Dewitz, Harald Wagner, Christina Bechtner, Michael Weigel, Hans-Christian Kolberg, Thomas Decker, Jörg Thomalla, Tobias Hesse, Nadia Harbeck, Jan Schröder Jens-Uwe Blohmer, Marc Wolf Sütterlin, Renske Altena, Chang-Fang Chiu, Shin-Cheh Chen, Ming-Feng Hou, Yuan-Ching Chang, Shang-Hung Chen, Shou-Tung Chen, Chiun-Sheng Huang, Dah-Cherng Yeh, Jyh-Cherng Yu, Ling-Ming Tseng, Wei-Pang Chung, Audrey Mailliez, Thierry Petit, Suzette Delaloge, Christelle Lévy, Philippe Dalivoust, Jean-Marc Extra, Marie-Ange Mouret-Reynier, Anne-Claire Hardy-Bessard, Hélène Simon, Tiffenn L'Haridon, Alice Mege, Sylvie Giacchetti, Camille Chakiba-Brugere, Alain Gratet, Virginie Pottier, Jean-Marc Ferrero, Isabelle Tennevet, Christophe Perrin, Jean-Luc Canon, Sofie Joris, Zhimin Shao, Binghe Xu, ZeFei Jiang, Qiang Sun, Kunwei Shen, Da Pang, Jin Zhang, Shui Wang, Hongjian Yang, Ning Liao, Hong Zheng, Peifen Fu, Chuangui Song, Yongsheng Wang, Zhimin Fan, Cuizhi Geng, Olivier Tredan, László Landherr, Bella Kaufman, Rinat Yerushalmi, Beatrice Uziely, Pierfranco Conte, Claudio Zamagni, Giampaolo Bianchini, Michelino De Laurentiis, Carlo Tondini, Vittorio Gebbia, Mariangela Ciccarese, Tomasz Sarosiek, Jacek Mackiewicz, Anna Słowińska, Ewa Kalinka, Tomasz Huzarski, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Jee Hyun Kim, Keun Seok Lee, Yeon Hee Park, Kyoung Eun Lee, Yee Soo Chae, Eun Kyung Cho, Institut Català de la Salut, [Geyer CE Jr] NRG Oncology/NSABP Foundation, Pittsburgh, USA. Department of Medicine, UPMC Hillman Cancer Center, Pittsburgh, USA. [Garber JE] Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA. [Gelber RD] Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA. Harvard T.H. Chan School of Public Health, Boston, USA. Frontier Science Foundation, Boston, USA. [Yothers G] NRG Oncology/NSABP Foundation, Pittsburgh, USA. Department of Biostatistics, University of Pittsburgh, Pittsburgh, USA. [Taboada M] Oncology Biometrics Department, AstraZeneca, Macclesfield, UK. [Ross L] Department of Data Management, Frontier Science (Scotland), Kincraig, Scotland, UK. [Balmaña J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Medical Oncology, Public Health, Virology, Department of Psychology, Education and Child Studies, Internal Medicine, General Practice, and Child and Adolescent Psychiatry / Psychology

Subjects
Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Breast Neoplasms, Other subheadings::Other subheadings::/drug therapy [Other subheadings], olaparib, Article, breast cancer, SDG 3 - Good Health and Well-being, BRCA1/2, células::células germinativas [ANATOMÍA], Humans, Other subheadings::/therapeutic use [Other subheadings], Cells::Germ Cells [ANATOMY], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Otros calificadores::/uso terapéutico [Otros calificadores], BRCA1 Protein, PARP inhibition, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], adjuvant therapy, Hematology, Cèl·lules germinals, Germ Cells, Oncology, Mama - Càncer - Tractament, Phthalazines, Female, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS]
Abstract

Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Published
2022

18. A Phase 2 Study of the LSD1 Inhibitor Bomedemstat (IMG-7289) for the Treatment of Advanced Myelofibrosis (MF): Updated Results and Genomic Analyses

Author

Kristen M. Pettit, Harinder Gill, Abdulraheem Yacoub, Terrence Bradley, Aaron T. Gerds, Maciej Tatarczuch, Jake Shortt, Natasha Joan Curtin, James M. Rossetti, Kate Burbury, Adam J Mead, Joachim R Göthert, Steffen Koschmieder, Matt Reyer, Benjamin Siranosian, Georges Natsoulis, William S Stevenson, Joanne Ewing, Joseph M. Chacko, Elisa Rumi, Anna B. Halpern, Francesca Palandri, Nicola Vianelli, Francesco Passamonti, Ruben Mesa, Monia Marchetti, Claire Harrison, Alessandro M. Vannucchi, Justin Watts, David M Ross, Moshe Talpaz, and Hugh Young Rienhoff

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

19. Updated Results from the Momentum Phase 3 Study of Momelotinib (MMB) Versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor

Author

Aaron T. Gerds, Ruben Mesa, Alessandro M Vannucchi, Haifa Kathrin Al-Ali, David Lavie, Andrew Kuykendall, Sebastian Grosicki, Alessandra Iurlo, Yeow Tee Goh, Mihaela Lazaroiu, Miklos Egyed, Maria Laura Fox, Donal P. McLornan, Andrew Charles Perkins, Sung-Soo Yoon, Vikas Gupta, Jean-Jacques Kiladjian, Rafe Donahue, Jun Kawashima, and Srdan Verstovsek

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

20. Novel Data Analytics Identify Predictors of Quality-of-Life Trajectories in Patients with AML or High-Risk Myeloid Neoplasms

Author

Jordan Gauthier, Bianca Furtuna, Jacopo Mangiavacchi, Shahrzad Gholami, Juan Lavista Ferres, Rahul Dodhia, Amir T. Fathi, Andrew M. Brunner, Aaron T. Gerds, Mikkael A. Sekeres, Bruno C. Medeiros, Eunice S. Wang, Paul J Shami, Kehinde Adekola, Selina M. Luger, Maria R. Baer, David A Rizzieri, Tanya Wildes, Jamie L. Koprivnikar, Julie Smith, Mitchell A. Garrison, Kiarash Kojouri, Frederick R. Appelbaum, Mary-Elizabeth M. Percival, Stephanie J. Lee, and Mohamed L. Sorror

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

21. A Phase 2 Study of the LSD1 Inhibitor Bomedemstat (IMG-7289) for the Treatment of Essential Thrombocythemia (ET)

Author

Harinder Gill, Francesca Palandri, David M Ross, Tara Cochrane, Courtney Tate, Steven W Lane, Stephen R Larsen, Aaron T. Gerds, Anna B. Halpern, Jake Shortt, James M. Rossetti, Kristen M. Pettit, James Liang, Adam J Mead, Monia Marchetti, Alessandro M. Vannucchi, Andrew J Wilson, Joachim R Göthert, Merit Hanna, Francesco Passamonti, William S Stevenson, Claire Harrison, Moshe Talpaz, Nicola Vianelli, and Hugh Young Rienhoff

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

22. Efficacy and Safety of Add-on Parsaclisib to Ruxolitinib Therapy in Myelofibrosis Patients With Suboptimal Response to Ruxolitinib: Final Results From a Phase 2 Study

Author

Abdulraheem Yacoub, Uma Borate, Raajit K Rampal, Haris Ali, Eunice Wang, Aaron T. Gerds, Gabriela S. Hobbs, Marina Kremyanskaya, Elliott Winton, Casey O'Connell, Swati Goel, Stephen T Oh, Gary J. Schiller, Albert Assad, Sue Erickson-Viitanen, Feng Zhou, and Naval Daver

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

24. Pattern of somatic mutation changes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Author

Sanghee Hong, Lisa Rybicki, Carmelo Gurnari, Simona Pagliuca, Aiwen Zhang, Dawn Thomas, Valeria Visconte, Jibran Durrani, Ronald M. Sobecks, Matt Kalaycio, Aaron T. Gerds, Hetty E. Carraway, Sudipto Mukherjee, Mikkael A. Sekeres, Anjali S. Advani, Navneet S. Majhail, Betty K. Hamilton, Bhumika J. Patel, and Jaroslaw P. Maciejewski

Subjects
Leukemia, Myeloid, Acute, Transplantation, Myelodysplastic Syndromes, Mutation, Hematopoietic Stem Cell Transplantation, Humans, Hematology, Settore MED/15
Published
2022

25. Patterns of Diagnostic Evaluation and Determinants of Treatment in Older Patients With Non-transfusion Dependent Myelodysplastic Syndromes

Author

Sudipto Mukherjee, Weichuan Dong, Nicholas K Schiltz, Kurt C Stange, Jennifer Cullen, Aaron T Gerds, Hetty E Carraway, Abhay Singh, Anjali S Advani, Mikkael A Sekeres, and Siran M Koroukian

Subjects
Cancer Research, Oncology
Abstract

Background Older patients with myelodysplastic syndromes (MDS), particularly those with no or one cytopenia and no transfusion dependence, typically have an indolent course. Approximately, half of these receive the recommended diagnostic evaluation (DE) for MDS. We explored factors determining DE in these patients and its impact on subsequent treatment and outcomes. Patients and Methods We used 2011-2014 Medicare data to identify patients ≥66 years of age diagnosed with MDS. We used Classification and Regression Tree (CART) analysis to identify combinations of factors associated with DE and its impact on subsequent treatment. Variables examined included demographics, comorbidities, nursing home status, and investigative procedures performed. We conducted a logistic regression analysis to identify correlates associated with receipt of DE and treatment. Results Of 16 851 patients with MDS, 51% underwent DE. patients with MDS with no cytopenia (n = 3908) had the lowest uptake of DE (34.7%). Compared to patients with no cytopenia, those with any cytopenia had nearly 3 times higher odds of receiving DE [adjusted odds ratio (AOR), 2.81: 95% CI, 2.60-3.04] and the odds were higher for men than for women [AOR, 1.39: 95%CI, 1.30-1.48] and for Non-Hispanic Whites [vs. everyone else (AOR, 1.17: 95% CI, 1.06-1.29)]. The CART showed DE as the principal discriminating node, followed by the presence of any cytopenia for receiving MDS treatment. The lowest percentage of treatment was observed in patients without DE, at 14.6%. Conclusion In this select older patients with MDS, we identified disparities in accurate diagnosis by demographic and clinical factors. Receipt of DE influenced subsequent treatment but not survival.

Published
2023

26. Consensus Recommendations on Peripheral Blood Smear Review: Defining Curricular Standards and Fellow Competency

Author

Matthew L Chase, Reed Drews, Marc Zumberg, Leslie R Ellis, Erin G Reid, Aaron T Gerds, Alfred I Lee, Gabriela Hobbs, Jonathan Berry, and Jason A Freed

Subjects
Hematology
Abstract

Graduate medical education training in hematology in North America is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees routinely review peripheral blood smears (PBS) in providing clinical care. Competency in PBS review at graduation is required by the ACGME. However, there are no consensus guidelines on best practices surrounding PBS review, education, or competency. We describe the generation of proposed theory and the consensus recommendations developed through a multi-institutional focus group, developed using constructivist grounded theory and a modified nominal group technique. Eight academic hematologists, spanning classical and malignant hematology, enrolled and participated in two one-hour focus groups. All routinely worked with fellows and half had formally instructed trainees on PBS interpretation. Focus group data was analyzed using mixed methods techniques. Tenets of emerging theory were identified through inductive coding. Consensus recommendations (CR) were generated. Participants reviewed CRs in an iterative fashion until consensus was reached. Strong consensus was reached on multiple aspects of PBS education. All agreed that trainees should learn PBS review through a systematic approach. Group discussion focused on disorders of red and white blood cells. The diagnoses of acute leukemia and thrombotic microangiopathies were most commonly discussed, with specific emphasis being placed on disorders in which prompt recognition was required to avert significant patient morbidity. These CRs offer external validity to future research and curricular development for both PBS review and other visuospatial tasks in medical education.

Published
2023

30. Efficacy and Safety of Ruxolitinib for Treatment of Symptomatic Chronic Myelomonocytic Leukemia (CMML): Results of a Multicenter Phase II Clinical Trial

Author

Eric Padron, Sara M Tinsley-Vance, Amy E. DeZern, Hetty E. Carraway, Marlise R. Luskin, Gail J. Roboz, Onyee Chan, Meagan Horton, Aaron T. Gerds, David A. Sallman, Andrew Kuykendall, David Steensma, Maria E Balasis, Jeffrey E. Lancet, Mikkael A. Sekeres, and Rami S. Komrokji

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

35. Momelotinib (MMB) Long-Term Safety: Pooled Data from Three Phase 3 Randomized-Controlled Trials (RCTs)

Author

Srdan Verstovsek, Ruben Mesa, Vikas Gupta, David Lavie, Viviane Dubruille, Nathalie Cambier, Uwe Platzbecker, Marek Hus, Blanca Xicoy, Stephen T Oh, Jean-Jacques Kiladjian, Alessandro M Vannucchi, Aaron T. Gerds, Miklos Egyed, Jiri Mayer, Tomasz Sacha, Jun Kawashima, Marc Morris, Mei Huang, and Claire Harrison

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

37. Transfusion Independence Response As a Potential Surrogate for Overall Survival in Jaki-Experienced Patients with Myelofibrosis from Momentum

Author

Srdan Verstovsek, Stephen T Oh, Jean-Jacques Kiladjian, Uwe Platzbecker, Francesco Passamonti, Aaron T. Gerds, Alessandro M Vannucchi, Donal P. McLornan, Vikas Gupta, Sebastian Grosicki, Haifa Kathrin Al-Ali, David Lavie, Andrew Kuykendall, Sung-Eun Lee, Alessandra Iurlo, Luminita Ocroteala, Jun Kawashima, Rafe Donahue, Bryan Strouse, and Ruben Mesa

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

38. ANKRD26 Coding Variants in Myeloid Neoplasia

Author

Teodora Kuzmanovic, Metis Hasipek, Samuel Li, Thomas Laframboise, Valeria Visconte, Sunisa Kongkiatkamon, Seth J. Corey, Sudipto Mukherjee, Anjali Advani, Aaron T. Gerds, Yogenthiran Saunthararajah, Sophia R. Balderman, Abhay Singh Singh, Hetty E. Carraway, Niroshan Nadarajah, Manja Meggendorfer, Jaroslaw P. Maciejewski, and Bhumika J. Patel

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

39. Haploidentical Donor Transplantation with Posttransplantation Cyclophosphamide in Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Institutional Collaboration of 14 Centers

Author

Tania Jain, Hua-Ling Tsai, Hany Elmariah, Pankit Vachhani, Theodoros Karantanos, Sarah A Wall, Lukasz P. Gondek, Asad Bashey, Alla Keyzner, Michael R. Grunwald, Sameem Abedin, Kalyan VG Nadiminti, Madiha Iqbal, Aaron T. Gerds, Auro Viswabandya, Shannon R McCurdy, MHD Monzr M. Al Malki, Ravi Varadhan, Haris Ali, Vikas Gupta, Richard J. Jones, and Salman Otoukesh

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

41. Momelotinib reduces transfusion requirements in patients with myelofibrosis

Author

Ruben Mesa, Stephen T. Oh, Aaron T. Gerds, Vikas Gupta, John Catalano, Francisco Cervantes, Timothy Devos, Marek Hus, Jean-Jacques Kiladjian, Ewa Lech-Maranda, Donal McLornan, Jeanne Palmer, Uwe Platzbecker, Jacek Treliński, Kazuya Shimoda, Rafe Donahue, Koenraad D’Hollander, Mark Kowalski, and Srdan Verstovsek

Subjects
Cancer Research, Pyrimidines, Oncology, Primary Myelofibrosis, immune system diseases, hemic and lymphatic diseases, Benzamides, Humans, Hematology
Abstract

ispartof: LEUKEMIA & LYMPHOMA vol:63 issue:7 pages:1718-1722 ispartof: location:United States status: published

Published
2022

42. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM):results from an international, double-blind, randomised, controlled, phase 3 study

Author

Srdan Verstovsek, Aaron T Gerds, Alessandro M Vannucchi, Haifa Kathrin Al-Ali, David Lavie, Andrew T Kuykendall, Sebastian Grosicki, Alessandra Iurlo, Yeow Tee Goh, Mihaela C Lazaroiu, Miklos Egyed, Maria Laura Fox, Donal McLornan, Andrew Perkins, Sung-Soo Yoon, Vikas Gupta, Jean-Jacques Kiladjian, Nikki Granacher, Sung-Eun Lee, Luminita Ocroteala, Francesco Passamonti, Claire N Harrison, Barbara J Klencke, Sunhee Ro, Rafe Donahue, Jun Kawashima, Ruben Mesa, Adi Shacham Abulafia, Bjorn Andreasson, Anna Angona, Rosa Ayala, Soo-Mee Bang, Bruce Bank, Fiorenza Barraco, Eloise Beggiato, Fleur Samantha Benghiat, MassimiliaNo Bonifacio, Claire Bories, Gabriela Borsaru, Mette Brabrand, Andrei Braester, Andes Broliden, Veronika Buxhofer-Ausch, Nathalie Cambier, Marianna Caramella, Benjamin Carpentier, Nicola Cascavilla, Maria Giraldo Castellano, Hung Chang, Chih-Cheng Chen, June-Won Cheong, Yunsuk Choi, Philip Choi, Maria Teresa Corsetti, Isabel Montero Cuadrado, Julia Cunningham, Gandhi Laurent Damaj, Valerio De Stefano, Robert Delage, Regina Garcĺa Delgado, Jose Miguel Torregrosa Diaz, Péter Dombi, Viviane Dubruille, Miklós Egyed, Daniel El Fassi, Anna Elinder-Camburn, Elena Maria Elli, Martin Ellis, Carmen Fava, Salman Fazal, Angela Fleischman, Lynda Foltz, Laura Fox, Nashat Gabrail, Jose Valentĺn Garcĺa-Gutiérrez, Aaron Gerds, Stephane Girault, Heinz Gisslinger, Alexandru Gluvacov, Joachim Göthert, Evgeni (Evgueniy) Hadjiev (Hadzhiev), Kaoutar Hafraoui, Aryan Hamed, Claire Harrison, Hans Hasselbalch, Hanns Hauser, Mark Heaney, Holger Hebart, Jesus Maria Hernandez Rivas, Victor Higuero Saavedra, Christopher Hillis, Hsin-An Hou, Jonathan How, Daniel Huang, Marek Hus, Arpad Illés, Alessandro Isidori, Vadim Ivanov, Peter Johansson, Chul Won Jung, Ilya Kirgner, Maya Koren-Michowitz, Steffen Koschmieder, Szabolcs Ors Kosztolanyi, Natalia Kreiniz, Andrew Kuykendall, Jonathan Lambert, Kamel Laribi, Axelle Lascaux, Noa Lavie, Mihaela Lazaroiu, Michael Leahy, Ewa Lech-Maranda, Won Sik Lee, Ollivier Legrand, Roberto Lemoli, James Liang, Sung-Nam Lim, Michael Loschi, Alessandro Lucchesi, Ioan Macarie, Jean-Pierre Marolleau, Maurizio Martelli, Jiri Mayer, James McCloskey, Christopher McDermott, Brandon McMahon, Priyanka Mehta, Gábor Mikala, Dragana Milojkovic, Philippe Mineur, Elena Mishchenko, Joon Ho Moon, Zsolt Nagy, Srinivasan Narayanan, Casey O'Connell, Stephen Oh, Mario Ojeda-Uribe, Kiat Hoe Ong, Folashade Otegbeye, Jeanne Palmer, Fabrizio Pane, Andrea Patriarca, Giuseppe Pietrantuono, Mark Plander, Uwe Platzbecker, Ritam Prasad, Witold Prejzner, Tobias Rachow, Atanas Radinoff, László Rejtő, Ciro Rinaldi, Tadeusz Robak, Maria Angeles Fernandez Rodriguez, Aaron Ronson, David Ross, Tomasz Sacha, Parvis Sadjadian, Antonio Salar, Guillermo Sanz Santillana, Christof Scheid, Aline Schmidt, Marianne Tang Severinsen, Vera Stoeva, Paweł Szwedyk, Mario Tiribelli, Karolin Trautmann-Grill, Amy Trottier, Nikolay Tzvetkov, Janusz van Droogenbroeck, Alessandro Vannucchi, Nicola Vianelli, Nikolas von Bubnoff, Dominik Wolf, Dariusz Woszczyk, Tomasz Woźny, Tomasz Wróbel, Blanca Xicoy, and Su-Peng Yeh

Subjects
Anemia/drug therapy, Treatment Outcome, Double-Blind Method, Janus Kinase Inhibitors/therapeutic use, Danazol/adverse effects, Humans, Primary Myelofibrosis/complications, General Medicine
Abstract

BACKGROUND: Janus kinase (JAK) inhibitors approved for myelofibrosis provide spleen and symptom improvements but do not meaningfully improve anaemia. Momelotinib, a first-in-class inhibitor of activin A receptor type 1 as well as JAK1 and JAK2, has shown symptom, spleen, and anaemia benefits in myelofibrosis. We aimed to confirm the differentiated clinical benefits of momelotinib versus the active comparator danazol in JAK-inhibitor-exposed, symptomatic patients with anaemia and intermediate-risk or high-risk myelofibrosis.METHODS: MOMENTUM is an international, double-blind, randomised, controlled, phase 3 study that enrolled patients at 107 sites across 21 countries worldwide. Eligible patients were 18 years or older with a confirmed diagnosis of primary myelofibrosis or post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis. Patients were randomly assigned (2:1) to receive momelotinib (200 mg orally once per day) plus danazol placebo (ie, the momelotinib group) or danazol (300 mg orally twice per day) plus momelotinib placebo (ie, the danazol group), stratified by total symptom score (TSS; FINDINGS: 195 patients were randomly assigned to either the momelotinib group (130 [67%]) or danazol group (65 [33%]) and received study treatment in the 24-week randomised treatment period between April 24, 2020, and Dec 3, 2021. A significantly greater proportion of patients in the momelotinib group reported a 50% or more reduction in TSS than in the danazol group (32 [25%] of 130 vs six [9%] of 65; proportion difference 16% [95% CI 6-26], p=0·0095). The most frequent grade 3 or higher treatment-emergent adverse events with momelotinib and danazol were haematological abnormalities by laboratory values: anaemia (79 [61%] of 130 vs 49 [75%] of 65) and thrombocytopenia (36 [28%] vs 17 [26%]). The most frequent non-haematological grade 3 or higher treatment-emergent adverse events with momelotinib and danazol were acute kidney injury (four [3%] of 130 vs six [9%] of 65) and pneumonia (three [2%] vs six [9%]).INTERPRETATION: Treatment with momelotinib, compared with danazol, resulted in clinically significant improvements in myelofibrosis-associated symptoms, anaemia measures, and spleen response, with favourable safety. These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anaemia.FUNDING: Sierra Oncology.

Published
2023

43. Survival following relapse after allogeneic hematopoietic cell transplantation for acute leukemia and myelodysplastic syndromes in the contemporary era

Author

Ronald Sobecks, Deepa Jagadeesh, Faiz Anwer, Lisa Rybicki, Navneet S. Majhail, Brad Pohlman, Aaron T. Gerds, Sanghee Hong, Betty K. Hamilton, Matt Kalaycio, Donna Corrigan, Brian T. Hill, and Robert M. Dean

Subjects
Oncology, medicine.medical_specialty, Survival, Disease, Refractory, Recurrence, Acute lymphocytic leukemia, Internal medicine, medicine, Humans, Diseases of the blood and blood-forming organs, Relapse, RC254-282, Acute leukemia, business.industry, Siblings, Myelodysplastic syndromes, Hazard ratio, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hematology, General Medicine, medicine.disease, Post-transplant relapse, Allogeneic stem cell transplantation, Transplantation, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, RC633-647.5, business
Abstract

Objective/Background: Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Methods: We reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. In total, 115 adults with relapsed or refractory ALL (n = 17), AML (n = 67), and MDS (n = 31) at median 5 (range, 1–64) months after their first alloHCT in 2010–2018 were included. Results: Median follow-up was 19 (range, 6–80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p = .027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p = .003), presence of grade II–IV acute graft-versus-host disease before relapse (HR 2.46; p 12 months; HR 6.34; p 12 months; HR 3.16; p = .005) were adverse prognostic factors for post-relapse survival. Conclusion: Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.

Published
2021

44. Allogeneic blood or marrow transplantation with haploidentical donor and post-transplantation cyclophosphamide in patients with myelofibrosis: a multicenter study

Author

Amy E. DeZern, Bhagirathbhai Dholaria, Richard J. Jones, Vikas Gupta, Siddharth Kunte, Asad Bashey, Aaron T. Gerds, Anurag K. Singh, Michael R. Grunwald, Roni Tamari, Michael Ozga, Hany Elmariah, Auro Viswabandya, Lisa Rybicki, Alla Keyzner, Madiha Iqbal, Sameem Abedin, and Tania Jain

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, Neutrophils, medicine.medical_treatment, Splenectomy, Graft vs Host Disease, Gastroenterology, Article, Internal medicine, Humans, Transplantation, Homologous, Medicine, Cumulative incidence, Myelofibrosis, Aged, Bone Marrow Transplantation, Retrospective Studies, Neutrophil Engraftment, business.industry, Incidence (epidemiology), Retrospective cohort study, Hematology, Middle Aged, Myeloablative Agonists, medicine.disease, Treatment Outcome, surgical procedures, operative, medicine.anatomical_structure, Oncology, Primary Myelofibrosis, Female, Bone marrow, Neoplasm Recurrence, Local, business, medicine.drug
Abstract

We report the results from a multicenter retrospective study of 69 adult patients who underwent haploidentical blood or marrow transplantation (haplo-BMT) with post-transplantation cyclophosphamide (PTCy) for chronic phase myelofibrosis. The median age at BMT was 63 years (range, 41-74). Conditioning regimens were reduced intensity in 54% and nonmyeloablative in 39%. Peripheral blood grafts were used in 86%. The median follow-up was 23.1 months (range, 1.6-75.7). At 3 years, the overall survival, relapse-free survival (RFS), and graft-versus-host-disease (GVHD)-free-RFS were 72% (95% CI 59-81), 44% (95% CI 29-59), and 30% (95% CI 17-43). Cumulative incidences of non-relapse mortality and relapse were 23% (95% CI 14-34) and 31% (95% CI 17-47) at 3 years. Spleen size ≥22 cm or prior splenectomy (HR 6.37, 95% CI 2.02-20.1, P = 0.002), and bone marrow grafts (HR 4.92, 95% CI 1.68-14.4, P = 0.004) were associated with increased incidence of relapse. Cumulative incidence of acute GVHD grade 3-4 was 10% at 3 months and extensive chronic GVHD was 8%. Neutrophil engraftment was reported in 94% patients, at a median of 20 days (range, 14-70). In conclusion, haplo-BMT with PTCy is feasible in patients with myelofibrosis. Splenomegaly ≥22 cm and bone marrow grafts were associated with a higher incidence of relapse in this study.

Published
2021

45. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph(+) acute lymphoblastic leukemia

Author

Anjali S. Advani, Anna Moseley, Kristen M. O’Dwyer, Brent L. Wood, Jae Park, Matthew Wieduwilt, Deepa Jeyakumar, George Yaghmour, Ehab L. Atallah, Aaron T. Gerds, Susan M. O'Brien, Jane L. Liesveld, Megan Othus, Mark Litzow, Richard M. Stone, Elad Sharon, and Harry P. Erba

Subjects
Pediatric, Lymphoid Neoplasia, Childhood Leukemia, Pediatric Cancer, Dasatinib, Evaluation of treatments and therapeutic interventions, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Vaccine Related, Treatment Outcome, Rare Diseases, Orphan Drug, Clinical Research, 6.1 Pharmaceuticals, 80 and over, Humans, Prednisone, Aged, Cancer
Abstract

Novel treatment strategies are needed for the treatment of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell–engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414.

Published
2022

46. An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm AML patients

Author

Mohamed Lotfy, Sorror, Ted A, Gooley, Barry E, Storer, Aaron T, Gerds, Mikkael A, Sekeres, Bruno C, Medeiros, Eunice S, Wang, Paul J, Shami, Kehinde U A, Adekola, Selina M, Luger, Maria R, Baer, David A, Rizzieri, Tanya, Wildes, Jamie, Koprivnikar, Julie, Smith, Mitchell, Garrison, Kiarash, Kojouri, Tammy A, Schuler, Wendy M, Leisenring, Lynn, Onstad, Pamela S, Becker, Jeannine S, McCune, Stephanie J, Lee, Brenda M, Sandmaier, Frederick R, Appelbaum, and Elihu, Estey

Abstract

We designed a prospective, observational study enrolling patients presenting for treatment of AML at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), function and geriatric health, in 6 groups: 1) the entire cohort, 2) ≥65 years old, 3) high comorbidity burden, 4) intermediate cytogenetic-risk, 5) adverse cytogenetic-risk, and 6) first complete remission with or without measurable residual disease. Patient health and preferences were assessed eight times across 2 years. Time-dependent regression models were used. Among 692 evaluable patients, 46% received HCT with 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality in the entire group and most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity-burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in all groups. While function, social life, performance status, and depressive symptoms were better for those selected for HCT compared to those who were not, these health advantages were lost after receiving HCT. Recipients and non-recipients of HCT similarly ranked and expected cure as main goal of therapy, while physicians expected more cure for the formers. Accounting for health impairments negate survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is due mostly to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT.

Published
2022

47. Myeloproliferative Neoplasms, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology

Author

Aaron T. Gerds, Jason Gotlib, Haris Ali, Prithviraj Bose, Andrew Dunbar, Amro Elshoury, Tracy I. George, Krishna Gundabolu, Elizabeth Hexner, Gabriela S. Hobbs, Tania Jain, Catriona Jamieson, Paul R. Kaesberg, Andrew T. Kuykendall, Yazan Madanat, Brandon McMahon, Sanjay R. Mohan, Kalyan V. Nadiminti, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Lindsay Rein, Rachel Salit, Brady L. Stein, Moshe Talpaz, Pankit Vachhani, Martha Wadleigh, Sarah Wall, Dawn C. Ward, Mary Anne Bergman, and Cindy Hochstetler

Subjects
Adult, Myeloproliferative Disorders, Oncology, Primary Myelofibrosis, Humans, Medical Oncology, Polycythemia Vera, Thrombocythemia, Essential
Abstract

The classic Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.

Published
2022

48. Integrated Human and Murine Clinical Study Establishes Clinical Efficacy of Ruxolitinib in Chronic Myelomonocytic Leukemia

Author

Amy E. DeZern, Alan F. List, Jeffrey E. Lancet, Hannah Newman, Eric Padron, Maria E. Balasis, Mikkael A. Sekeres, Rami S. Komrokji, Anthony M. Hunter, Qianxing Mo, Traci Kruer, Sandrine Niyongere, Markus Ball, Christopher Letson, Aaron T. Gerds, Gail J. Roboz, David A. Sallman, Hailing Zhang, Onyee Chan, David P. Steensma, and William Dominguez-Viqueira

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Ruxolitinib, Drug Evaluation, Preclinical, Chronic myelomonocytic leukemia, Malignancy, Mice, Monocytosis, Internal medicine, Nitriles, Biomarkers, Tumor, medicine, Animals, Humans, Janus Kinase Inhibitors, Adverse effect, Myeloproliferative neoplasm, Aged, Aged, 80 and over, Clinical Trials as Topic, business.industry, Leukemia, Myelomonocytic, Chronic, Middle Aged, Prognosis, medicine.disease, Clinical trial, Leukemia, Pyrimidines, Treatment Outcome, Mutation, Cytokines, Pyrazoles, Female, business, medicine.drug
Abstract

Purpose: Chronic myelomonocytic leukemia (CMML) is a rare leukemia characterized by peripheral monocytosis with no disease-modifying therapies. CMML cells are uniquely hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) and robustly engraft in immunocompromised mice that secrete human cytokines. To leverage these unique biological features, we conducted an integrated human and murine study evaluating ruxolitinib, a JAK1/2 inhibitor that potently downregulates intracellular GM-CSF signaling. Patients and Methods: A total of 50 patients with WHO-defined CMML were enrolled in this open-label, multi-institution phase I/II clinical study, with a ruxolitinib dose of 20 mg twice daily studied in phase II. In parallel, 49 patient-derived xenografts (PDX) derived from 13 study participants were generated and randomized to receive ruxolitinib or vehicle control. Results: The most common grade 3/4 treatment-related toxicities observed were anemia (10%) and thrombocytopenia (6%). The clinical overall response rate was 38% by Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) International Working Group (IWG) criteria and 43% of patients with baseline splenomegaly achieved a spleen response. Profiling of cytokine levels and somatic mutations at baseline failed to identify predictive biomarkers. PDX models derived from screening samples of study participants recapitulated responses seen in humans, particularly spleen responses, and corroborated ruxolitinib's clinical efficacy in a randomized murine study not feasible in human trials. Conclusions: Ruxolitinib demonstrated clinical efficacy and an acceptable adverse event profile in patients with CMML, identifying a potential novel therapeutic in this rare malignancy. Furthermore, this study demonstrates proof of concept that PDX modeling can recapitulate responses of patients treated on clinical trial and represents a novel correlative study that corroborates clinical efficacy seen in humans. See related commentary by Shastri and Adrianzen-Herrera, p. 6069

Published
2021

49. Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis

Author

Ruben Mesa, Claire Harrison, Stephen T. Oh, Aaron T. Gerds, Vikas Gupta, John Catalano, Francisco Cervantes, Timothy Devos, Marek Hus, Jean-Jacques Kiladjian, Ewa Lech-Maranda, Donal McLornan, Alessandro M. Vannucchi, Uwe Platzbecker, Mei Huang, Bryan Strouse, Barbara Klencke, and Srdan Verstovsek

Subjects
Cancer Research, OUTCOMES, Science & Technology, INTERNATIONAL WORKING GROUP, IMPACT, Anemia, Hematology, Janus Kinase 2, DISEASE, HEPCIDIN, Pyrimidines, Oncology, Primary Myelofibrosis, AVAILABLE THERAPY, Benzamides, Nitriles, Humans, Janus Kinase Inhibitors, RUXOLITINIB, ANEMIA, Protein Kinase Inhibitors, Life Sciences & Biomedicine, Retrospective Studies
Abstract

Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR = 0.98 [0.59, 1.62]; LFS HR = 0.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR = 0.474, p = 0.0001; SIMPLIFY-2 HR = 0.226, p = 0.0005). Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR = 0.323; p p

Published
2022

50. Targeting the PI3K pathway in myeloproliferative neoplasms

Author

Aaron T Gerds, Niccolo Bartalucci, Albert Assad, and Abdulraheem Yacoub

Subjects
Phosphatidylinositol 3-Kinases, Myeloproliferative Disorders, Oncology, Neoplasms, Humans, Pharmacology (medical), Janus Kinase 2, Phosphatidylinositol 3-Kinase, Protein Kinase Inhibitors
Abstract

Decreasing efficacy over time and initial suboptimal response to Janus kinase (JAK) inhibitors such as ruxolitinib in a subset of patients are critical clinical challenges associated with myeloproliferative neoplasms (MPNs), primarily myelofibrosis.The role of phosphatidylinositol-3 kinase (PI3K) in MPN disease progression and treatment resistance and as a potential therapeutic target in patients who experience loss of response to JAK inhibition is discussed. Understanding the complex signaling networks involved in the pathogenesis of MPNs has identified potentially novel therapeutic targets and treatment strategies, such as inhibiting other signaling pathways in addition to the JAK/signal transducer and activator of transcription (STAT) pathway. PI3K plays a crucial role downstream of JAK signaling in rescuing tumor cell proliferation, with PI3Kδ being particularly important in hematologic malignancies. Concurrent targeting of both PI3K and JAK/STAT pathways may offer an innovative therapeutic strategy to maximize efficacy.Based on our understanding of the underlying mechanisms and the role of PI3K pathway signaling in the loss of response or resistance to JAK inhibitor treatment and initial results from clinical studies, the combination of parsaclisib (PI3Kδ inhibitor) and ruxolitinib holds great clinical potential. If confirmed in larger clinical trials, parsaclisib may provide more treatment options and improve clinical outcomes for patients with MPNs.

Published
2022

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