Year: 2025
Type: article
Study design: Observational Study
Abstract: T cells engineered with CD19-directed chimeric antigen receptors (CD19 CAR) T cells have become standard treatment for patients with high risk, relapsed or refractory (R/R) large B-cell lymphomas (LBCL). However, outcomes in patients with rare subsets of LBCL, such as primary mediastinal large B-cell lymphoma (PBMCL), have not been well characterized. The impact of prior immune checkpoint inhibitor (ICI) treatment, commonly used to treat R/R PMBCL, is also unknown. To address these gaps, we retrospectively analyzed CIBMTR registry data including PMBCL patients undergoing CD19 CAR T-cell therapy per standard-of-care. A total of 135 PMBCL adults from 66 centers were included. Median age at the time of CAR T-cell therapy was 32. Thirty-nine patients (28.9%) had received an ICI prior to CAR T-cell therapy. The best overall and complete response (CR) rates after CD19 CAR T-cell therapy were 79% and 67.7%, respectively. The 2-year progression-free (PFS) and overall survival (OS) were 58.6% (95% CI, 49.7-67.3) and 80.8% (95% CI, 72.6-87.8), respectively. The 2-year cumulative incidence (CI) of relapse and non-relapse mortality (NRM) were 36% (95% CI, 27.8-44.7) and 5.4% (95% CI, 1.9-10.5), respectively. We observed grade ≥ 3 CRS and ICANS in 6.1% and 14.7%, respectively. Prior ICI exposure was associated with lower 2-year CI of relapse (ICI-exposed, 21.7%; ICI-naïve, 41.6%; p = 0.03) and higher 2-year NRM (ICI-exposed, 11.7%; ICI-naïve, 2.8%; p = 0.03). We could not confirm statistically different PFS (p = 0.19) or OS (p = 0.26) between ICI-exposed and ICI-naïve patients. CD19 CAR T-cell therapy led to high rates of durable responses in PMBCL patients with low rates of severe toxicities.
Source: American Journal of Hematology
DOI: 10.1002/ajh.70033
Authors: Jordan Gauthier, Kwang W. Ahn, Jinalben Patel, Qinghua Lian, Sherif Badawy, Mitchell S. Cairo, Julio Delgado, Natalie Grover, Bradley Haverkos, Marcos de Lima, Adriana Malone, Alberto Mussetti, Yago Nieto, Attaphol Pawarode, Laurie Pearson, Melhem Solh, Anna Sureda, Aung M. Tun, Kitsada Wudhikarn, Samuel Yamshon, Mazyar Shadman, Cameron J. Turtle, Mehdi Hamadani, Alex F. Herrera
Institutions: University of Washington, Fred Hutch Cancer Center, Medical College of Wisconsin, Northwestern University, Lurie Children's Hospital, Westchester Medical Center, New York Medical College, Maria Fareri Children's Hospital, Hospital Clínic de Barcelona, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, University of Colorado Denver, The Ohio State University, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, The University of Texas MD Anderson Cancer Center, University of Michigan, Michigan Medicine, University of Massachusetts Chan Medical School, UMass Memorial Medical Center, Northside Hospital, University of Kansas, Chulalongkorn University, Weill Cornell Medicine, The University of Sydney, Royal North Shore Hospital, City Of Hope National Medical Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Amgen, Bristol-Myers Squibb, Pfizer, Astellas Pharma US, Sanofi, Gilead Sciences, Alexion Pharmaceuticals, Celgene, Novartis Pharmaceuticals Corporation, CSL Behring, StemCyte, Regeneron Pharmaceuticals, Actinium Pharmaceuticals, Jazz Pharmaceuticals, Angiocrine Bioscience, bluebird bio, Incyte, Omeros Corporation, Kiadis Pharma, Astellas Pharma, Servier, Health Resources and Services Administration, Genentech, Takeda Oncology, Sanofi Genzyme, Pharmacyclics, Legend Biotech, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Daiichi Sankyo Europe
Awards: G1360182821, G1387388519, G2551907125, G3540884004, G5039041663, G5356860631, G5478485217, G5804481516, G6238506038, G6659488911, G6979277618, G7949979095, G8006577219, G8666848461, G8871973681, G8876996369, A Data Resource for Blood and Marrow Transplants and Adoptive Cellular Therapy Research
OpenAlex ID: W4413101514