CAR T cells or allogeneic transplantation as standard of care for advanced large B-cell lymphoma: an intent-to-treat comparison

被引:30
作者
Dreger, Peter [1 ]
Dietrich, Sascha [1 ]
Schubert, Maria-Luisa [1 ]
Selberg, Lorenz [1 ]
Bondong, Andrea [1 ]
Wegner, Mandy [1 ]
Stadtherr, Peter [1 ]
Kimmich, Christoph [1 ]
Kosely, Florentina [1 ]
Schmitt, Anita [1 ]
Pavel, Petra [2 ]
Liebers, Nora [1 ]
Luft, Thomas [1 ]
Hegenbart, Ute [1 ]
Radujkovic, Aleksandar [1 ]
Ho, Anthony Dick [1 ]
Mueller-Tidow, Carsten [1 ]
Schmitt, Michael [1 ]
机构
[1] Heidelberg Univ, Dept Med 5, Neuenheimer Feld 410, D-69120 Heidelberg, Germany
[2] Inst Clin Transfus Med & Cell Therapy, Heidelberg, Germany
关键词
OPEN-LABEL; RITUXIMAB; OUTCOMES; THERAPY; DISEASE; SAFETY; SURVIVAL; EFFICACY; RELAPSE; INDEX;
D O I
10.1182/bloodadvances.2020003036
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
CD19-directed chimeric antigen receptor (CAR) T-cell treatment has evolved as standard of care (SOC) for multiply relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, its potential benefit over allogeneic hematopoietic cell transplantation (alloHCT) remains unclear. We compared outcomes with both types of cellular immunotherapy (CI) by intention to treat (ITT). Eligble were all patients with R/R LBCL and institutional tumor board decision recommending SOC CAR T-cell treatment between July 2018 and February 2020, or alloHCT between January 2004 and February 2020. Primary end point was overall survival (OS) from indication. Altogether, 41 and 60 patients for whom CAR T cells and alloHCT were intended, respectively, were included. In both cohorts, virtually all patients had active disease at indication. CI was recommended as part of second-line therapy for 21 alloHCT patients but no CAR T-cell patients. Median OS from indication was 475 days with CAR T cells vs 285 days with alloHCT (P = .88) and 222 days for 39 patients for whom alloHCT beyond second line was recommended (P = .08). Of CAR T-cell and alloHCT patients, 73% and 65%, respectively, proceeded to CI. After CI, 12-month estimates for nonrelapse mortality, relapse incidence, progression-free survival, and OS for CAR T cells vs alloHCT were 3% vs 21% (P = .04), 59% vs 44% (P = .12), 39% vs 33% (P = .97), and 68% vs 54% (P = .32), respectively. In conclusion, CAR T-cell outcomes were not inferior to alloHCT outcomes, whether measured by ITT or from CI administration, supporting strategies preferring CAR T cells over alloHCT as first CI for multiply R/R LBCL.
引用
收藏
页码:6157 / 6168
页数:12
相关论文
共 42 条
[1]   Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma [J].
Abramson, Jeremy S. ;
McGree, Brianne ;
Noyes, Sarah ;
Plummer, Sean ;
Wong, Curtis ;
Chen, Yi-Bin ;
Palmer, Edwin ;
Albertson, Tina ;
Ferry, Judith A. ;
Arrillaga-Romany, Isabel C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (08) :783-784
[2]   Defining the Intensity of Conditioning Regimens: Working Definitions [J].
Bacigalupo, Andrea ;
Ballen, Karen ;
Rizzo, Doug ;
Giralt, Sergio ;
Lazarus, Hillard ;
Ho, Vincent ;
Apperley, Jane ;
Slavin, Shimon ;
Pasquini, Marcelo ;
Sandmaier, Brenda M. ;
Barrett, John ;
Blaise, Didier ;
Lowski, Robert ;
Horowitz, Mary .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2009, 15 (12) :1628-1633
[3]   Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion [J].
Bishop, Michael R. ;
Maziarz, Richard T. ;
Waller, Edmund K. ;
Jaeger, Ulrich ;
Westin, Jason R. ;
McGuirk, Joseph P. ;
Fleury, Isabelle ;
Holte, Harald ;
Borchmann, Peter ;
del Corral, Christopher ;
Tiwari, Ranjan ;
Anak, Oezlem ;
Awasthi, Rakesh ;
Pacaud, Lida ;
Romanov, Vadim V. ;
Schuster, Stephen J. .
BLOOD ADVANCES, 2019, 3 (14) :2230-2236
[4]   Outcomes of patients with large B-cell lymphomas and progressive disease following CD19-specific CAR T-cell therapy [J].
Chow, Victor A. ;
Gopal, Ajay K. ;
Maloney, David G. ;
Turtle, Cameron J. ;
Smith, Stephen D. ;
Ujjani, Chaitra S. ;
Shadman, Mazyar ;
Cassaday, Ryan D. ;
Till, Brian G. ;
Tseng, Yolanda D. ;
Warren, Edus H. ;
Shustov, Andrei R. ;
Menon, Manoj P. ;
Bhark, Sandra ;
Acharya, Utkarsh H. ;
Mullane, Erin ;
Hannan, Lindsay M. ;
Voutsinas, Jenna M. ;
Gooley, Ted A. ;
Lynch, Ryan C. .
AMERICAN JOURNAL OF HEMATOLOGY, 2019, 94 (08) :E209-E213
[5]   Diffuse large B-cell lymphoma with primary treatment failure: Ultra-high risk features and benchmarking for experimental therapies [J].
Costa, Luciano J. ;
Maddocks, Kami ;
Epperla, Narendranath ;
Reddy, Nishitha M. ;
Karmali, Reem ;
Umyarova, Elvira ;
Bachanova, Veronika ;
Costa, Cristiana ;
Glenn, Martha J. ;
Chavez, Julio C. ;
Calzada, Oscar ;
Lansigan, Frederick ;
Nasheed, Hossain ;
Barta, Stefan K. ;
Zhou, Zheng ;
Jaglal, Michael ;
Chhabra, Saurabh ;
Hernandez-Ilizaliturri, Francisco ;
Xavier, Ana C. ;
Mehta, Amitkumar ;
Peker, Deniz ;
Forero-Torres, Andreas ;
Al-Mansour, Zeina ;
Evens, Andrew M. ;
Cohen, Jonathon B. ;
Flowers, Christopher R. ;
Fenske, Timothy S. ;
Hamadani, Mehdi .
AMERICAN JOURNAL OF HEMATOLOGY, 2017, 92 (02) :161-170
[6]   Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [J].
Crump, Michael ;
Neelapu, Sattva S. ;
Farooq, Umar ;
Van den Neste, Eric ;
Kuruvilla, John ;
Westin, Jason ;
Link, Brian K. ;
Hay, Annette ;
Cerhan, James R. ;
Zhu, Liting ;
Boussetta, Sami ;
Feng, Lei ;
Maurer, Matthew J. ;
Navale, Lynn ;
Wiezorek, Jeff ;
Go, William Y. ;
Gisselbrecht, Christian .
BLOOD, 2017, 130 (16) :1800-1808
[7]   Cellular Immunotherapy for Refractory Diffuse Large B Cell Lymphoma in the Chimeric Antigen Receptor-Engineered T Cell Era: Still a Role for Allogeneic Transplantation? [J].
Dreger, Peter ;
Fenske, Timothy S. ;
Montoto, Silvia ;
Pasquini, Marcelo C. ;
Sureda, Anna ;
Hamadani, Mehdi .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2020, 26 (04) :E77-E85
[8]   Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019 [J].
Duarte, Rafael F. ;
Labopin, Myriam ;
Bader, Peter ;
Basak, Grzegorz W. ;
Bonini, Chiara ;
Chabannon, Christian ;
Corbacioglu, Selim ;
Dreger, Peter ;
Dufour, Carlo ;
Genneryl, Andrew R. ;
Kuball, Juergen ;
Lankester, Arjan C. ;
Lanza, Francesco ;
Montoto, Silvia ;
Nagler, Arnon ;
de Latour, Regis Peffault ;
Snowden, John A. ;
Styczynski, Jan ;
Yakoub-Agha, Ibrahim ;
Kroeger, Nicolaus ;
Mohty, Mohamad ;
Albert, Michael ;
Alexander, Tobias ;
Averbuch, Dina ;
Baron, Frederic ;
Bazarbachi, Eli ;
Beksac, Meral ;
Brissot, Eolia ;
Bug, Gesine ;
Cesaro, Simone ;
Chalandon, Yves ;
Ciceri, Fabo ;
Czerw, Tomasz ;
Dazzi, Francesco ;
Esteve, Jordi ;
Fleischhauer, Katarina ;
Garderet, Laurent ;
Giebel, Sebastian ;
Gil, Lidia ;
Gilleece, Maria ;
Gorin, Norbert-Claude ;
Hayden, Patrick ;
Halter, Jorg ;
Hernandez Boluda, Juan C. ;
Hudecek, Michael ;
Kleinschmidt, Katharina ;
Kenyon, Michelle ;
Koenecke, Christian ;
Locatelli, Franco ;
Malard, Florent .
BONE MARROW TRANSPLANTATION, 2019, 54 (10) :1525-1552
[9]   Postrelapse survival in diffuse large B-cell lymphoma after therapy failure following autologous transplantation [J].
Epperla, Narendranath ;
Badar, Talha ;
Szabo, Aniko ;
Vaughn, John ;
Borson, Steve ;
Saini, Neeraj Y. ;
Patel, Romil D. ;
Shah, Nirav N. ;
Hamadani, Mehdi ;
Ahmed, Sairah ;
Cashen, Amanda F. ;
Fenske, Timothy S. .
BLOOD ADVANCES, 2019, 3 (11) :1661-1669
[10]   Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation [J].
Fenske, Timothy S. ;
Ahn, Kwang W. ;
Graff, Tara M. ;
DiGilio, Alyssa ;
Bashir, Qaiser ;
Kamble, Rammurti T. ;
Ayala, Ernesto ;
Bacher, Ulrike ;
Brammer, Jonathan E. ;
Cairo, Mitchell ;
Chen, Andy ;
Chen, Yi-Bin ;
Chhabra, Saurabh ;
D'Souza, Anita ;
Farooq, Umar ;
Freytes, Cesar ;
Ganguly, Siddhartha ;
Hertzberg, Mark ;
Inwards, David ;
Jaglowski, Samantha ;
Kharfan-Dabaja, Mohamed A. ;
Lazarus, Hillard M. ;
Nathan, Sunita ;
Pawarode, Attaphol ;
Perales, Miguel-Angel ;
Reddy, Nishitha ;
Seo, Sachiko ;
Sureda, Anna ;
Smith, Sonali M. ;
Hamadani, Mehdi .
BRITISH JOURNAL OF HAEMATOLOGY, 2016, 174 (02) :235-248