Ruxolitinib as the first post-steroid treatment for acute and chronic graft-versus-host disease

被引:4
作者
Algeri, Mattia [1 ,2 ]
Becilli, Marco [1 ]
Locatelli, Franco [1 ,3 ,4 ]
机构
[1] IRCCS Bambino Gesu Childrens Hosp, Dept Haematol Oncol & Cell & Gene Therapy, Rome, Italy
[2] Magna Grecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy
[3] Univ Cattolica Sacro Cuore, Dept Life Sci & Publ Hlth, Rome, Italy
[4] Univ Cattolica Sacro Cuore, IRCCS Bambino Gesu Childrens Hosp, Dept Haematol Oncol & Cell & Gene Therapy, Piazza St Onofrio, I-400165 Rome, Italy
关键词
acute-GvHD; chronic-GvHD; corticosteroid-dependent GvHD; corticosteroid-refractory GvHD; HSCT; JAK1; 2; inhibitor; REACH studies; ruxolitinib; STEM-CELL TRANSPLANTATION; TOTAL-BODY IRRADIATION; REGULATORY T-CELLS; DONOR B-CELLS; ACUTE GVHD; PROPHYLAXIS; INHIBITOR; INCB018424; CD4(+); SAFETY;
D O I
10.1080/1744666X.2023.2249230
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IntroductionAcute and chronic graft-versus-host disease (GvHD) are potentially life-threatening complications occurring after allogeneic stem cell transplantation (allo-HSCT). Although steroids represent the first-line treatment for both conditions, in those patients who do not adequately benefit from steroid therapy, standardized treatment algorithms are lacking. In recent years, ruxolitinib has emerged as the most promising agent for the second-line therapy of steroid-refractory (SR)-GvHD.Areas coveredThis review will summarize the biological properties and the mechanistic aspects that justify the therapeutic role of ruxolitinib in GvHD. In addition, current treatment options for SR-GvHD will be briefly discussed. Finally, results of the most relevant clinical trials on the use of ruxolitinib for SR-GvHD will be analyzed, with a particular focus on two phase-III randomized trials in which ruxolitinib demonstrated its superiority in comparison with the best available therapy.Expert opinionRuxolitinib has considerably improved the outcome of patients with SR-acute/chronic-GvHD and should be regarded as the standard-of-care option when corticosteroids fail or cannot be tapered. Nevertheless, a number of questions still remain unanswered and significant room for improvement exists. Additional observations derived from a longer follow-up will certainly increase our expertise in the management of this powerful therapy.
引用
收藏
页码:1299 / 1313
页数:15
相关论文
共 103 条
[1]   Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation [J].
Abedin, Sameem ;
McKenna, Edward ;
Chhabra, Saurabh ;
Pasquini, Marcelo ;
Shah, Nirav N. ;
Jerkins, James ;
Bairn, Arielle ;
Runaas, Lyndsey ;
Longo, Walter ;
Drobyski, William ;
Hari, Parameswaran N. ;
Hamadani, Mehdi .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2019, 25 (08) :1689-1694
[2]   Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD [J].
Alho, Ana C. ;
Kim, Haesook T. ;
Chammas, Marie J. ;
Reynolds, Carol G. ;
Matos, Tiago R. ;
Forcade, Edouard ;
Whangbo, Jennifer ;
Nikiforow, Sarah ;
Cutler, Corey S. ;
Koreth, John ;
Ho, Vincent T. ;
Armand, Philippe ;
Antin, Joseph H. ;
Alyea, Edwin P. ;
Lacerda, Joao F. ;
Soiffer, Robert J. ;
Ritz, Jerome .
BLOOD, 2016, 127 (05) :646-657
[3]   Increased BCR responsiveness in B cells from patients with chronic GVHD [J].
Allen, Jessica L. ;
Tata, Prasanthi V. ;
Fore, Matthew S. ;
Wooten, Jenna ;
Rudra, Sharmistha ;
Deal, Allison M. ;
Sharf, Andrew ;
Hoffert, Todd ;
Roehrs, Philip A. ;
Shea, Thomas C. ;
Serody, Jonathan S. ;
Richards, Kristy L. ;
Jagasia, Madan ;
Lee, Stephanie J. ;
Rizzieri, David ;
Horwitz, Mitchell E. ;
Chao, Nelson J. ;
Sarantopoulos, Stefanie .
BLOOD, 2014, 123 (13) :2108-2115
[4]   Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody-Begelomab [J].
Bacigalupo, Andrea ;
Angelucci, Emanuele ;
Raiola, Anna Maria ;
Varaldo, Riccardo ;
Di Grazia, Carmen ;
Gualandi, Francesca ;
Benedetti, Edoardo ;
Risitano, Antonio ;
Musso, Maurizio ;
Zallio, Francesco ;
Ciceri, Fabio ;
Chiusolo, Patrizia ;
Sica, Simona ;
Rambaldi, Alessandro ;
Bonifazi, Francesca ;
Parma, Matteo ;
Martino, Massimo ;
Onida, Francesco ;
Iori, Anna Paola ;
Selleri, Carmine ;
Borghero, Carlo ;
Bertaina, Alice ;
Prezioso, Lucia ;
Algeri, Mattia ;
Locatelli, Franco .
BONE MARROW TRANSPLANTATION, 2020, 55 (08) :1580-1587
[5]   JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects [J].
Banerjee, Shubhasree ;
Biehl, Ann ;
Gadina, Massimo ;
Hasni, Sarfaraz ;
Schwartz, Daniella M. .
DRUGS, 2017, 77 (05) :521-546
[6]   Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen [J].
Betts, Brian C. ;
Abdel-Wahab, Omar ;
Curran, Shane A. ;
St Angelo, Erin T. ;
Koppikar, Priya ;
Heller, Glenn ;
Levine, Ross L. ;
Young, James W. .
BLOOD, 2011, 118 (19) :5330-5339
[7]   Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease [J].
Braun, Lukas M. ;
Zeiser, Robert .
FRONTIERS IN IMMUNOLOGY, 2021, 12
[8]   Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects [J].
Carniti, Cristiana ;
Gimondi, Silvia ;
Vendramin, Antonio ;
Recordati, Camilla ;
Confalonieri, Davide ;
Bermema, Anisa ;
Corradini, Paolo ;
Mariotti, Jacopo .
CLINICAL CANCER RESEARCH, 2015, 21 (16) :3740-3749
[9]  
CHEBI, About us
[10]   Pharmacologic Blockade of JAK1/JAK2 Reduces GvHD and Preserves the Graft-Versus-Leukemia Effect [J].
Choi, Jaebok ;
Cooper, Matthew L. ;
Alahmari, Bader ;
Ritchey, Julie ;
Collins, Lynne ;
Holt, Matthew ;
DiPersio, John F. .
PLOS ONE, 2014, 9 (10)