Characteristics and recognition of early infections in patients treated with commercial anti-CD19 CAR-T cells

被引:28
作者
Beyar-Katz, Ofrat [1 ,2 ]
Kikozashvili, Nino [1 ,2 ]
Bar On, Yael [1 ,2 ]
Amit, Odelia [1 ,2 ]
Perry, Chava [2 ,3 ]
Avivi, Irit [2 ,3 ]
Gold, Ronit [1 ]
Herishanu, Yair [2 ,3 ]
Benyamini, Noam [2 ,3 ]
Duek, Adrian [4 ]
Ben-Ami, Ronen [2 ,5 ]
Shasha, David [2 ,5 ]
Ram, Ron [1 ,2 ]
机构
[1] Tel Aviv Sourasky Med Ctr, BMT Unit, Tel Aviv, Israel
[2] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
[3] Tel Aviv Sourasky Med Ctr, Dept Hematol, Tel Aviv, Israel
[4] Univ Hosp Assuta Ashdod, Hematol Inst, Ashdod, Israel
[5] Tel Aviv Sourasky Med Ctr, Infect Dis Unit, Tel Aviv, Israel
关键词
CAR-T cells; infection; lymphoma; RISK-FACTORS; COMPLICATIONS; THERAPY; HODGKIN;
D O I
10.1111/ejh.13712
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The characteristics of infections following chimeric antigen receptor T (CAR-T) cells targeting CD19 in real-word population are obscure. We analyzed infections' characteristics in the first month among consecutive patients with diffuse large B-cell lymphoma (DLBCL) (n = 60, median age, 69.3 years), treated with commercial CAR-T cells. ECOG performance status (PS) was 2-3 in most patients (58%). Infections were observed in 45% of patients (16, 27%, bacterial infections, and 14, 23%, viral infections). Bacterial infection included clinically documented infection in 7 (Pneumonia, n = 5; periodontal infection, n = 1; and cellulitis, n = 1) and microbiology documented infection (MDI) in 9 patients (Gram-negative rod, n = 5; Gram-positive cocci, n = 3, bacteremia; polymicrobial, n = 1). The most common viral infection was cytomegalovirus (CMV) reactivation (n = 10, 17%) leading to initiation of anti-CMV treatment in 6 (60%) among these patients. None had CMV disease. In univariate analysis, immune effector cell-associated neurotoxicity syndrome (ICANS) was associated with higher incidence of bacterial infection (OR=4.5, P = .018), while there was a trend for lower incidence of bacterial infections in patients with chemosensitive disease to bridging therapy (OR=0.375, P = .074). Age or PS was not associated with increased risk of bacterial infection. Increase in C-reactive protein (CRP) prior to fever onset was associated with microbiologically documented infections. We conclude that infections are common in the first month following CAR-T-cell administration, however, were not increased in elderly patients or those presenting with poorer PS. Increase in CRP prior to fever onset could support infection over cytokine release syndrome.
引用
收藏
页码:52 / 60
页数:9
相关论文
共 16 条
[1]   Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study [J].
Abramson, Jeremy S. ;
Palomba, M. Lia ;
Gordon, Leo I. ;
Lunning, Matthew A. ;
Wang, Michael ;
Arnason, Jon ;
Mehta, Amitkumar ;
Purev, Enkhtsetseg ;
Maloney, David G. ;
Andreadis, Charalambos ;
Sehgal, Alison ;
Solomon, Scott R. ;
Ghosh, Nilanjan ;
Albertson, Tina M. ;
Garcia, Jacob ;
Kostic, Ana ;
Mallaney, Mary ;
Ogasawara, Ken ;
Newhall, Kathryn ;
Kim, Yeonhee ;
Li, Daniel ;
Siddiqi, Tanya .
LANCET, 2020, 396 (10254) :839-852
[2]   Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification [J].
Cheson, Bruce D. ;
Fisher, Richard I. ;
Barrington, Sally F. ;
Cavalli, Franco ;
Schwartz, Lawrence H. ;
Zucca, Emanuele ;
Lister, T. Andrew .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3059-+
[3]   Risk factors and prognostic scale for cytomegalovirus (CMV) infection in CMV-seropositive patients after allogeneic hematopoietic cell transplantation [J].
Cohen, L. ;
Yeshurun, M. ;
Shpilberg, O. ;
Ram, R. .
TRANSPLANT INFECTIOUS DISEASE, 2015, 17 (04) :510-517
[4]   Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy [J].
Hill, Joshua A. ;
Li, Daniel ;
Hay, Kevin A. ;
Green, Margaret L. ;
Cherian, Sindhu ;
Chen, Xueyan ;
Riddell, Stanley R. ;
Maloney, David G. ;
Boeckh, Michael ;
Turtle, Cameron J. .
BLOOD, 2018, 131 (01) :121-130
[5]   Risk factors and characteristics of blood stream infections in patients with newly diagnosed multiple myeloma [J].
Huang, Chun-Teng ;
Liu, Chia-Jen ;
Ko, Po-Shen ;
Liu, Han-Tsung ;
Yu, Yuan-Bin ;
Hsiao, Liang-Tsai ;
Gau, Jyh-Pyng ;
Tzeng, Cheng-Hwai ;
Chiou, Tzeon-Jye ;
Liu, Jin-Hwang ;
Yang, Muh-Hwa ;
Huang, Ling-Ju ;
Liu, Chun-Yu .
BMC INFECTIOUS DISEASES, 2017, 17
[6]   Infection Complications after Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma [J].
Korell, Felix ;
Schubert, Maria-Luisa ;
Sauer, Tim ;
Schmitt, Anita ;
Derigs, Patrick ;
Weber, Tim Frederik ;
Schnitzler, Paul ;
Mueller-Tidow, Carsten ;
Dreger, Peter ;
Schmitt, Michael .
CANCERS, 2021, 13 (07)
[7]   ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells [J].
Lee, Daniel W. ;
Santomasso, Bianca D. ;
Locke, Frederick L. ;
Ghobadi, Armin ;
Turtle, Cameron J. ;
Brudno, Jennifer N. ;
Maus, Marcela, V ;
Park, Jae H. ;
Mead, Elena ;
Pavletic, Steven ;
Go, William Y. ;
Eldjerou, Lamis ;
Gardner, Rebecca A. ;
Frey, Noelle ;
Curran, Kevin J. ;
Peggs, Karl ;
Pasquini, Marcelo ;
DiPersio, John F. ;
van den Brink, Marcel R. M. ;
Komanduri, Krishna, V ;
Grupp, Stephan A. ;
Neelapu, Sattva S. .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2019, 25 (04) :625-638
[8]   Infectious Complications Associated with CAR T-Cell Therapy [J].
Mikkilineni, Lekha ;
Shahani, Shilpa ;
Yates, Bonnie ;
Steinberg, Seth M. ;
Palmore, Tara ;
Nussenblatt, Veronique ;
Lee, Daniel W. ;
Kaplan, Rosandra N. ;
Mackall, Crystal L. ;
Fry, Terry J. ;
Gea-Banacloche, Juan ;
Jerussi, Theresa ;
Kochenderfer, James N. ;
Shah, Nirali N. .
BLOOD, 2019, 134
[9]   Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma [J].
Neelapu, S. S. ;
Locke, F. L. ;
Bartlett, N. L. ;
Lekakis, L. J. ;
Miklos, D. B. ;
Jacobson, C. A. ;
Braunschweig, I. ;
Oluwole, O. O. ;
Siddiqi, T. ;
Lin, Y. ;
Timmerman, J. M. ;
Stiff, P. J. ;
Friedberg, J. W. ;
Flinn, I. W. ;
Goy, A. ;
Hill, B. T. ;
Smith, M. R. ;
Deol, A. ;
Farooq, U. ;
McSweeney, P. ;
Munoz, J. ;
Avivi, I. ;
Castro, J. E. ;
Westin, J. R. ;
Chavez, J. C. ;
Ghobadi, A. ;
Komanduri, K. V. ;
Levy, R. ;
Jacobsen, E. D. ;
Witzig, T. E. ;
Reagan, P. ;
Bot, A. ;
Rossi, J. ;
Navale, L. ;
Jiang, Y. ;
Aycock, J. ;
Elias, M. ;
Chang, D. ;
Wiezorek, J. ;
Go, W. Y. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (26) :2531-2544
[10]   Outcomes of older patients in ZUMA-1, a pivotal study of axicabtagene ciloleucel in refractory large B-cell lymphoma [J].
Neelapu, Sattva S. ;
Jacobson, Caron A. ;
Oluwole, Olalekan O. ;
Munoz, Javier ;
Deol, Abhinav ;
Miklos, David B. ;
Bartlett, Nancy L. ;
Braunschweig, Ira ;
Jiang, Yizhou ;
Kim, Jenny J. ;
Zheng, Lianqing ;
Rossi, John M. ;
Locke, Frederick L. .
BLOOD, 2020, 135 (23) :2106-2109