Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma

被引:12
作者
Costa, Bruno Almeida [1 ,2 ]
Flynn, Jessica [3 ]
Nishimura, Noriko [4 ,5 ]
Devlin, Sean M. [3 ]
Farzana, Tasmin [1 ]
Rajeeve, Sridevi [1 ,4 ]
Chung, David J. [1 ,5 ,6 ]
Landau, Heather J. [1 ,5 ,6 ]
Lahoud, Oscar B. [1 ,5 ,6 ]
Scordo, Michael [1 ,5 ,6 ]
Shah, Gunjan L. [1 ,5 ,6 ]
Hassoun, Hani [4 ,6 ]
Maclachlan, Kylee [4 ,6 ]
Hultcrantz, Malin [4 ,6 ]
Korde, Neha [4 ,6 ]
Lesokhin, Alexander M. [1 ,4 ,6 ]
Shah, Urvi A. [4 ,6 ]
Tan, Carlyn R. [4 ,6 ]
Giralt, Sergio A. [1 ,5 ,6 ]
Usmani, Saad Z. [1 ,4 ,5 ,6 ]
Nath, Karthik [1 ]
Mailankody, Sham [1 ,4 ,6 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, Cellular Therapy Serv, New York, NY 10065 USA
[2] Icahn Sch Med Mt Sinai, Mt Sinai Morningside West, Dept Med, New York, NY USA
[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA
[4] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, New York, NY 10065 USA
[5] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, Dept Med, New York, NY USA
[6] Weill Cornell Med, Dept Med, New York, NY 10065 USA
关键词
SINGLE-ARM; APOPTOSIS;
D O I
10.1038/s41408-024-01048-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.
引用
收藏
页数:8
相关论文
共 44 条
[21]   Regulatory and Mechanistic Actions of Glucocorticoids on T and Inflammatory Cells [J].
Liberman, Ana C. ;
Budzinski, Maia L. ;
Sokn, Clara ;
Gobbini, Romina Paula ;
Steininger, Anja ;
Arzt, Eduardo .
FRONTIERS IN ENDOCRINOLOGY, 2018, 9
[22]   A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy [J].
Liu, Dora ;
Ahmet, Alexandra ;
Ward, Leanne ;
Krishnamoorthy, Preetha ;
Mandelcorn, Efrem D. ;
Leigh, Richard ;
Brown, Jacques P. ;
Cohen, Albert ;
Kim, Harold .
ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, 2013, 9
[23]   Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia [J].
Liu, Shuangyou ;
Deng, Biping ;
Yin, Zhichao ;
Pan, Jing ;
Lin, Yuehui ;
Ling, Zhuojun ;
Wu, Tong ;
Chen, Dong ;
Chang, Alex H. ;
Gao, Zhiyong ;
Song, Yanzhi ;
Zhao, Yongqiang ;
Tong, Chunrong .
BLOOD CANCER JOURNAL, 2020, 10 (02)
[24]   Patterns and Safety of Glucocorticosteroids Use Following CD19 CAR-T Cell Therapy for B- Cell Lymphoma [J].
Luttwak, Efrat ;
Flynn, Jessica R. ;
Devlin, Sean M. ;
Cassanello, Giulio ;
Corona, Magdalena ;
Dahi, Parastoo B. ;
De Abia, Alejandro Luna ;
Fein, Joshua ;
Giralt, Sergio A. ;
Landego, Ivan ;
Lin, Richard J. ;
Palomba, Maria Lia ;
Parascondola, Allison ;
Park, Jae H. ;
Saldia, Amethyst ;
Scordo, Michael ;
Tomas, Ana Alarcon ;
Shah, Gunjan L. ;
Perales, Miguel-Angel ;
Salles, Gilles ;
Shouval, Roni .
BLOOD, 2023, 142
[25]   Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results [J].
Mailankody, Sham ;
Matous, Jeffrey V. ;
Chhabra, Saurabh ;
Liedtke, Michaela ;
Sidana, Surbhi ;
Oluwole, Olalekan O. ;
Malik, Shahbaz ;
Nath, Rajneesh ;
Anwer, Faiz ;
Cruz, Jose Carlos ;
Htut, Myo ;
Karski, Erin E. ;
Lovelace, Wade ;
Dillon, Myles ;
Butz, Eric ;
Ying, Wendy ;
Balakumaran, Arun ;
Kumar, Shaji K. .
NATURE MEDICINE, 2023, 29 (2) :422-429
[26]   GPRC5D-Targeted CAR T Cells for Myeloma [J].
Mailankody, Sham ;
Devlin, Sean M. M. ;
Landa, Jonathan ;
Nath, Karthik ;
Diamonte, Claudia ;
Carstens, Elizabeth J. J. ;
Russo, Douglas ;
Auclair, Romany ;
Fitzgerald, Lisa ;
Cadzin, Briana ;
Wang, Xiuyan ;
Sikder, Devanjan ;
Senechal, Brigitte ;
Bermudez, Vladimir P. P. ;
Purdon, Terence J. J. ;
Hosszu, Kinga ;
McAvoy, Devin P. P. ;
Farzana, Tasmin ;
Mead, Elena ;
Wilcox, Jessica A. A. ;
Santomasso, Bianca D. D. ;
Shah, Gunjan L. L. ;
Shah, Urvi A. A. ;
Korde, Neha ;
Lesokhin, Alexander ;
Tan, Carlyn R. R. ;
Hultcrantz, Malin ;
Hassoun, Hani ;
Roshal, Mikhail ;
Sen, Filiz ;
Dogan, Ahmet ;
Landgren, Ola ;
Giralt, Sergio A. A. ;
Park, Jae H. H. ;
Usmani, Saad Z. Z. ;
Riviere, Isabelle ;
Brentjens, Renier J. J. ;
Smith, Eric L. L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2022, 387 (13) :1196-1206
[27]   CAR T cell therapies for patients with multiple myeloma [J].
Mikkilineni, Lekha ;
Kochenderfer, James N. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2021, 18 (02) :71-84
[28]   Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy [J].
Morris, Emma C. ;
Neelapu, Sattva S. ;
Giavridis, Theodoros ;
Sadelain, Michel .
NATURE REVIEWS IMMUNOLOGY, 2022, 22 (02) :85-96
[29]   Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma [J].
Munshi, Nikhil C. ;
Anderson, Larry D., Jr. ;
Shah, Nina ;
Madduri, Deepu ;
Berdeja, Jesus ;
Lonial, Sagar ;
Raje, Noopur ;
Lin, Yi ;
Siegel, David ;
Oriol, Albert ;
Moreau, Philippe ;
Yakoub-Agha, Ibrahim ;
Delforge, Michel ;
Cavo, Michele ;
Einsele, Hermann ;
Goldschmidt, Hartmut ;
Weisel, Katja ;
Rambaldi, Alessandro ;
Reece, Donna ;
Petrocca, Fabio ;
Massaro, Monica ;
Connarn, Jamie N. ;
Kaiser, Shari ;
Patel, Payal ;
Huang, Liping ;
Campbell, Timothy B. ;
Hege, Kristen ;
San-Miguel, Jesus .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (08) :705-716
[30]   Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium [J].
Nastoupil, Loretta J. ;
Jain, Michael D. ;
Feng, Lei ;
Spiegel, Jay Y. ;
Ghobadi, Armin ;
Lin, Yi ;
Dahiya, Saurabh ;
Lunning, Matthew ;
Lekakis, Lazaros ;
Reagan, Patrick ;
Oluwole, Olalekan ;
McGuirk, Joseph ;
Deol, Abhinav ;
Sehgal, Alison R. ;
Goy, Andre ;
Hill, Brian T. ;
Vu, Khoan ;
Andreadis, Charalambos ;
Munoz, Javier ;
Westin, Jason ;
Chavez, Julio C. ;
Cashen, Amanda ;
Bennani, N. Nora ;
Rapoport, Aaron P. ;
Vose, Julie M. ;
Miklos, David B. ;
Neelapu, Sattva S. ;
Locke, Frederick L. .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (27) :3119-+