Treatment and outcomes of progression of disease post–CAR T-cell therapy in mantle cell lymphoma: a multicenter analysis
Year: 2025
Type: article
Study design: Observational Study
Abstract: ABSTRACT: The treatment patterns and clinical outcomes for patients experiencing progression of disease (POD) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR T-cell therapy for R/R MCL therapy across 15 international centers, and studied those experiencing POD post-CAR T-cell therapy in detail. We extracted clinical/treatment/pathologic variables, and associated these features with survival outcomes. In total, 384 patients received CAR T-cell therapy, and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR T-cell therapy infusion, and most (64%) patients with POD had complete response as best response to CAR T-cell therapy. Tumor features at POD included blastoid/pleomorphic morphology in 29 of 78 (37%) patients, and TP53 mutation in 21 of 41 (51%) patients. Following POD, 17 patients received no further therapy, 13 underwent local therapy, and 105 received systemic therapy. The most common first-line systemic therapies were chemo(immuno)therapy (22 patients; overall response rate [ORR], 40%), pirtobrutinib (17 patients; ORR, 36%), and bispecific antibodies (13 patients; ORR, 67%). Among patients experiencing POD, the median progression-free survival and overall survival (OS) were 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR T-cell therapy and short time from CAR T-cell therapy infusion to POD (<3 vs 3-6 vs >6 months), among other factors, were associated with inferior OS after POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR T-cell therapy for R/R MCL, and establish a benchmark for future investigations in this patient population.
Source: Blood Advances
Authors: Zachary D. Epstein-Peterson, Anath C. Lionel, Ashlee Joseph, Esther Drill, Suheil Albert Atallah-Yunes, Taylor R. Brooks, Elise A. Chong, Emeline R. Chong, Jamie Dela Cruz, Matthew J. Frank, Andrew Ip, Madiha Iqbal, Caron A. Jacobson, Manali K. Kamdar, Reem Karmali, Ofrat Beyar-Katz, Kami J. Maddocks, Matthew J. Matasar, Daniel McLoughlin, Reid W. Merryman, Javier L. Munoz, Rohini Navalekar, Joanna Rhodes, Peter A. Riedell, Christine E. Ryan, Gilles Salles, Craig S. Sauter, Yazeed Sawalha, Samanvaya Sharma, Roni Shouval, Navika Shukla, Dylan Therwhanger, Herman van Besien, Ben Varon, Yucai Wang, Samuel Yamshon, Andrew D. Zelenetz, Maria Lia Palomba, Preetesh Jain, Anita Kumar
Institutions: Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The University of Texas MD Anderson Cancer Center, Mayo Clinic, Cleveland Clinic, Hospital of the University of Pennsylvania, Abramson Cancer Center, University of Pennsylvania, Dana-Farber Cancer Institute, Stanford Medicine, Stanford University, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack Meridian School of Medicine, Mayo Clinic in Florida, University of Colorado Cancer Center, University of Colorado Denver, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Technion – Israel Institute of Technology, Rambam Health Care Campus, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University Hospital, The Ohio State University, Rutgers Cancer Institute, Mayo Clinic Hospital, University of Chicago
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4412984567