부산대학교 도서관

Summary 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. Author Affiliation: (a) Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (b) Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA (c) Department of Hematology, University of Florence, Florence, Italy (d) Center of Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Florence, Italy (e) Krukenberg Cancer Center, University Hospital of Halle, Halle, Germany (f) Department of Hematology and Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel (g) Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA (h) Department of Hematology and Cancer Prevention, Medical University of Silesia, Katowice, Poland (i) Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy (j) Department of Haematology, Singapore General Hospital, Singapore (k) Department of Hematology, Policlinica de Diagnostic Rapid Brasov, Brasov, Romania (l) Department of Hematology, Somogy County Mór Kaposi General Hospital, Kaposvár, Hungary (m) Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Barcelona, Spain (n) Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK (o) Department of Haematology, Alfred Hospital, Monash University, Melbourne, Australia (p) Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea (q) Department of Medicine, Princess Margaret Cancer Centre, Toronto, ON, Canada (r) Université de Paris, AP-HP, Hoôpital Saint-Louis, Centre d'Investigations Cliniques, INSERM, CIC1427, Paris, France (s) Department of Hematology, Ziekenhuis Netwerk Antwerpen, Antwerp, Belgium (t) Department of Laboratory Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea (u) Filantropia Hospital, Craiova, Romania (v) Department of Medicine and Surgery, University of Insubria, Varese, Italy (w) Sierra Oncology, San Mateo, CA, USA (x) Mays Cancer Center, UT Health San Antonio MD Anderson, San Antonio, TX, USA * Correspondence to: Prof Srdan Verstovsek, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (footnote)[Dagger] A complete list of principal investigators for the MOMENTUM study is provided in the Byline: Prof Srdan Verstovsek, MD [sverstov@mdanderson.org] (a), Aaron T Gerds, MD (b), Prof Alessandro M Vannucchi, MD (c,d), Haifa Kathrin Al-Ali, MD (e), David Lavie, MD (f), Andrew T Kuykendall, MD (g), Sebastian Grosicki, MD (h), Alessandra Iurlo, MD (i), Prof Yeow Tee Goh, MD (j), Mihaela C Lazaroiu, MD (k), Prof Miklos Egyed, MD (l), Maria Laura Fox, MD (m), Donal McLornan, PhD (n), Prof Andrew Perkins, MD (o), Prof Sung-Soo Yoon, MD (p), Vikas Gupta, MD (q), Prof Jean-Jacques Kiladjian, MD (r), Nikki Granacher, MD (s), Sung-Eun Lee, MD (t), Luminita Ocroteala, MD (u), Prof Francesco Passamonti, MD (v), Prof Claire N Harrison, DM (n), Barbara J Klencke, MD (w), Sunhee Ro, PhD (w), Rafe Donahue, PhD (w), Jun Kawashima, MD (w), Prof Ruben Mesa, MD (x), Adi Shacham Abulafia, Haifa Kathrin Al-Ali, 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, Yeow Tee Goh, Joachim Göthert, Nikki Granacher, Sebastian Grosicki, Vikas Gupta, 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, Alessandra Iurlo, Vadim Ivanov, Peter Johansson, Chul Won Jung, Jean-Jacques Kiladjian, Ilya Kirgner, Maya Koren-Michowitz, Steffen Koschmieder, Szabolcs Ors Kosztolanyi, Natalia Kreiniz, Andrew Kuykendall, Jonathan Lambert, Kamel Laribi, Axelle Lascaux, Noa Lavie, David Lavie, Mihaela Lazaroiu, Michael Leahy, Ewa Lech-Maranda, Sung-Eun Lee, 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, Donal McLornan, Brandon McMahon, Priyanka Mehta, Ruben Mesa, Gábor Mikala, Dragana Milojkovic, Philippe Mineur, Elena Mishchenko, Joon Ho Moon, Zsolt Nagy, Srinivasan Narayanan, Casey O'Connell, Luminita Ocroteala, Stephen Oh, Mario Ojeda-Uribe, Kiat Hoe Ong, Folashade Otegbeye, Jeanne Palmer, Fabrizio Pane, Francesco Passamonti, Andrea Patriarca, Andrew Perkins, Giuseppe Pietrantuono, Mark Plander, Uwe Platzbecker, Ritam Prasad, Witold Prejzner, Tobias Rachow, Atanas Radinoff, László Rejto, 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, Pawel Szwedyk, Mario Tiribelli, Karolin Trautmann-Grill, Amy Trottier, Nikolay Tzvetkov, Janusz van Droogenbroeck, Alessandro Vannucchi, Srdan Verstovsek, Nicola Vianelli, Nikolas von Bubnoff, Dominik Wolf, Dariusz Woszczyk, Tomasz Wozny, Tomasz Wróbel, Blanca Xicoy, Su-Peng Yeh, Sung-Soo Yoon