A research center's experience of T-cell-redirecting therapies in triple-class refractory multiple myeloma

被引:5
作者
Puertas, Borja [1 ]
Fernandez-Sanchez, Adolfo [1 ]
Alejo, Elena [1 ]
Rey-Bua, Beatriz [1 ]
Martin-Lopez, Ana A. [1 ]
Perez-Lopez, Estefania [1 ]
Lopez-Parra, Miriam [1 ]
Lopez-Corral, Lucia [1 ]
Gutierrez-Gutierrez, Norma C. [1 ]
Garcia-Sanz, Ramon [1 ]
Puig, Noemi [1 ]
Gonzalez-Calle, Veronica [1 ]
Mateos, Maria-Victoria [1 ]
机构
[1] Univ Hosp Salamanca, Canc Res Ctr IBMCC, Ctr Invest Biomed Red Canc, Hematol Dept,Inst Invest Biomed Salamanca, Salamanca, Spain
关键词
MINIMAL RESIDUAL DISEASE; OUTCOMES; ANTIBODY;
D O I
10.1182/bloodadvances.2024012773
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The efficacies of chimeric antigen receptor T cells (CAR-Ts) and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-Ts and 37 received BiAbs. CAR-Ts produced a higher overall response rate (ORR) than BiAbs (97.1% vs 56.8%, P = .002). After a median of followup of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs 10.8 months; P = .090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs 22.6 months; P = .021). BiAbs after CAR-Ts yielded a higher ORR and longer PFS2 than did nonredirecting T-cell therapies after CAR-Ts (ORR: 87.5% vs 50.0%; PFS2: 22.9 vs 12.4 months). By contrast, BiAbs after BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the nonredirecting T-cell therapies (ORR: 28.6%; PFS2: 8.1 months). Although this is a pooled analysis of different trials with different products and the patient profile is different for CAR-Ts and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, although the PFS was similar with the 2 approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real- word experience.
引用
收藏
页码:3478 / 3487
页数:10
相关论文
共 38 条
[1]   Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial [J].
Bahlis, Nizar J. ;
Costello, Caitlin L. ;
Raje, Noopur S. ;
Levy, Moshe Y. ;
Dholaria, Bhagirathbhai ;
Solh, Melhem ;
Tomasson, Michael H. ;
Damore, Michael A. ;
Jiang, Sibo ;
Basu, Cynthia ;
Skoura, Athanasia ;
Chan, Edward M. ;
Trudel, Suzanne ;
Jakubowiak, Andrzej ;
Gasparetto, Cristina ;
Chu, Michael P. ;
Dalovisio, Andrew ;
Sebag, Michael ;
Lesokhin, Alexander M. .
NATURE MEDICINE, 2023, 29 (10) :2570-+
[2]   Upregulation of Senescent/Exhausted Phenotype of CAR T Cells and Induction of Both Treg and Myeloid Suppressive Cells Correlate with Reduced Response to CAR T Cell Therapy in Relapsed/Refractory B Cell Malignancies [J].
Beider, Katia ;
Besser, Michal J. ;
Schachter, Jacob ;
Grushchenko-Polaq, Ania Hava ;
Voevoda, Valeria ;
Wolf, Idit ;
Ostrovsky, Olga ;
Jacoby, Elad ;
Shimoni, Avichai ;
Nagler, Arnon .
BLOOD, 2019, 134
[3]   Ciltacabtagene autoleucel, a B-cell maturation antigendirected chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study [J].
Berdeja, Jesus G. ;
Madduri, Deepu ;
Usmani, Saad Z. ;
Jakubowiak, Andrzej ;
Agha, Mounzer ;
Cohen, Adam D. ;
Stewart, A. Keith ;
Hari, Parameswaran ;
Htut, Myo ;
Lesokhin, Alexander ;
Deol, Abhinav ;
Munshi, Nikhil C. ;
O'Donnell, Elizabeth ;
Avigan, David ;
Singh, Indrajeet ;
Zudaire, Enrique ;
Yeh, Tzu-Min ;
Allred, Alicia J. ;
Olyslager, Yunsi ;
Banerjee, Arnob ;
Jackson, Carolyn C. ;
Goldberg, Jenna D. ;
Schecter, Jordan M. ;
Deraedt, William ;
Zhuang, Sen Hong ;
Infante, Jeffrey ;
Geng, Dong ;
Wu, Xiaoling ;
Carrasco-Alfonso, Marlene J. ;
Akram, Muhammad ;
Hossain, Farah ;
Rizvi, Syed ;
Fan, Frank ;
Lin, Yi ;
Martin, Thomas ;
Jagannath, Sundar .
LANCET, 2021, 398 (10297) :314-324
[4]   Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody [J].
Chari, Ajai ;
Minnema, Monique C. ;
Berdeja, Jesus G. ;
Oriol, Albert ;
van de Donk, Niels W. C. J. ;
Rodriguez-Otero, Paula ;
Askari, Elham ;
Mateos, Maria-Victoria ;
Costa, Luciano J. ;
Caers, Jo ;
Verona, Raluca ;
Girgis, Suzette ;
Yang, Shiyi ;
Goldsmith, Rachel B. ;
Yao, Xiang ;
Pillarisetti, Kodandaram ;
Hilder, Brandi W. ;
Russell, Jeffery ;
Goldberg, Jenna D. ;
Krishnan, Amrita .
NEW ENGLAND JOURNAL OF MEDICINE, 2022, 387 (24) :2232-2244
[5]   Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents [J].
Cohen, Adam D. ;
Mateos, Maria-Victoria ;
Cohen, Yael C. ;
Rodriguez-Otero, Paula ;
Paiva, Bruno ;
van de Donk, Niels W. C. J. ;
Martin, Thomas ;
Suvannasankha, Attaya ;
De Braganca, Kevin C. ;
Corsale, Christina ;
Schecter, Jordan M. ;
Varsos, Helen ;
Deraedt, William ;
Wang, Liwei ;
Vogel, Martin ;
Roccia, Tito ;
Xu, Xiaoying ;
Mistry, Pankaj ;
Zudaire, Enrique ;
Akram, Muhammad ;
Nesheiwat, Tonia ;
Pacaud, Lida ;
Avivi, Irit ;
San-Miguel, Jesus .
BLOOD, 2023, 141 (03) :219-230
[6]   A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen x CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma [J].
D'Souza, Anita ;
Shah, Nina ;
Rodriguez, Cesar ;
Voorhees, Peter M. ;
Weisel, Katja ;
Bueno, Orlando F. ;
Pothacamury, Rajvineeth K. ;
Freise, Kevin J. ;
Yue, Susan ;
Ross, Jeremy A. ;
Polepally, Akshanth R. ;
Talati, Chetasi ;
Lee, Shane ;
Jin, Ziyi ;
Buelow, Ben ;
Vij, Ravi ;
Kumar, Shaji .
JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (31) :3576-+
[7]   Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy [J].
Ferreri, Christopher J. J. ;
Hildebrandt, Michelle A. T. ;
Hashmi, Hamza ;
Shune, Leyla O. O. ;
McGuirk, Joseph P. P. ;
Sborov, Douglas W. W. ;
Wagner, Charlotte B. B. ;
Kocoglu, M. Hakan ;
Rapoport, Aaron ;
Atrash, Shebli ;
Voorhees, Peter M. M. ;
Khouri, Jack ;
Dima, Danai ;
Afrough, Aimaz ;
Kaur, Gurbakhash ;
Anderson, Larry D. D. ;
Simmons, Gary ;
Davis, James A. A. ;
Kalariya, Nilesh ;
Peres, Lauren C. C. ;
Lin, Yi ;
Janakiram, Murali ;
Nadeem, Omar ;
Alsina, Melissa ;
Locke, Frederick L. L. ;
Sidana, Surbhi ;
Hansen, Doris K. K. ;
Patel, Krina K. K. ;
Puglianini, Omar Alexis Castaneda .
BLOOD CANCER JOURNAL, 2023, 13 (01)
[8]   Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma [J].
Flores-Montero, J. ;
Sanoja-Flores, L. ;
Paiva, B. ;
Puig, N. ;
Garcia-Sanchez, O. ;
Boettcher, S. ;
van der Velden, V. H. J. ;
Perez-Moran, J-J ;
Vidriales, M-B ;
Garcia-Sanz, R. ;
Jimenez, C. ;
Gonzalez, M. ;
Martinez-Lopez, J. ;
Corral-Mateos, A. ;
Grigore, G-E ;
Fluxa, R. ;
Pontes, R. ;
Caetano, J. ;
Sedek, L. ;
del Canizo, M-C ;
Blade, J. ;
Lahuerta, J-J ;
Aguilar, C. ;
Barez, A. ;
Garcia-Mateo, A. ;
Labrador, J. ;
Leoz, P. ;
Aguilera-Sanz, C. ;
San-Miguel, J. ;
Mateos, M-V ;
Durie, B. ;
van Dongen, J. J. M. ;
Orfao, A. .
LEUKEMIA, 2017, 31 (10) :2094-2103
[9]   Impact of high-risk disease on the efficacy of chimeric antigen receptor T-cell therapy for multiple myeloma: a meta-analysis of 723 patients [J].
Gagelmann, Nico ;
Ayuk, Francis A. ;
Klyuchnikov, Evgeny ;
Wolschke, Christine ;
Berger, Susanna Carolina ;
Kroeger, Nicolaus .
HAEMATOLOGICA, 2023, 108 (10) :2799-2802
[10]   Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy [J].
Gandhi, Ujjawal H. ;
Cornell, Robert F. ;
Lakshman, Arjun ;
Gahvari, Zhubin J. ;
McGehee, Elizabeth ;
Jagosky, Megan H. ;
Gupta, Ridhi ;
Varnado, William ;
Fiala, Mark A. ;
Chhabra, Saurabh ;
Malek, Ehsan ;
Mansour, Joshua ;
Paul, Barry ;
Barnstead, Alyssa ;
Kodali, Saranya ;
Neppalli, Amarendra ;
Liedtke, Michaela ;
Narayana, Swapna ;
Godby, Kelly N. ;
Kang, Yubin ;
Kansagra, Ankit ;
Umyarova, Elvira ;
Scott, Emma C. ;
Hari, Parameswaran ;
Vij, Ravi ;
Usmani, Saad Z. ;
Callander, Natalie S. ;
Kumar, Shaji K. ;
Costa, Luciano J. .
LEUKEMIA, 2019, 33 (09) :2266-2275