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Observational Study
. 2025 Oct;100(10):1792-1802.
doi: 10.1002/ajh.70033. Epub 2025 Aug 11.

CD19 CAR T-Cell Therapy for Primary Mediastinal Large B-Cell Lymphoma: A CIBMTR Analysis

Jordan Gauthier  1   2 , Kwang W Ahn  3   4 , Jinalben Patel  4 , Qinghua Lian  3 , Sherif Badawy  5 , Mitchell S Cairo  6 , Julio Delgado  7 , Natalie Grover  8 , Bradley Haverkos  9 , Marcos de Lima  10 , Adriana Malone  11 , Alberto Mussetti  12 , Yago Nieto  13 , Attaphol Pawarode  14 , Laurie Pearson  15 , Melhem Solh  16 , Anna Sureda  17 , Aung M Tun  18 , Kitsada Wudhikarn  19 , Samuel Yamshon  20 , Mazyar Shadman  1   2 , Cameron J Turtle  21   22 , Mehdi Hamadani  23 , Alex F Herrera  24
Affiliations
Observational Study

CD19 CAR T-Cell Therapy for Primary Mediastinal Large B-Cell Lymphoma: A CIBMTR Analysis

Jordan Gauthier et al. Am J Hematol. 2025 Oct.

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.

Keywords: CD19 CAR T‐cell therapy; CIBMTR; adoptive T‐cell therapy; non‐Hodgkin lymphoma; primary mediastinal large B‐cell lymphoma.

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Conflict of interest statement

Disclosure of conflict of interest:

Jordan Gauthier reports Research Funding: Sobi, Bristol Myers Squibbs, Angiocrine Bioscience, Faron Pharmaceuticals, CARGO Therapeutics, CytoAgents; Ad Hoc Advisory Board: Bristol Myers Squibbs, Sobi, Legend Biotech, Janssen, Kite Pharma, MorphoSys; Independent Data Review Committee: Century Therapeutics.

Mitchell S. Cairo reports Research Funding: AbbVie, Merck, Pfizer, Spectrum, Miltenyi, Servier, Jazz, Omeros, Alexion; Speakers Bureau: Amgen and JazzNatalie Grover reports Research Funding from BMS, Cabaletta, Affimed, Poseida and Regeneron; DSMB: Novartis, Consultancy: Genentech, Regeneron, ADC Therapeutics, and BMS.

Marcos de Lima reports reports Consultancy: Abbvie; Independent Data Review Committee: Pfizer, Autolus.

Alberto Mussetti reports Honoraria: Takeda, BMS , Gilead, Sanofi; Ad Hoc Advisory Board: Merck, Jazz Pharma; Research Funding, Atara, Takeda, Gilead.

Laurie Pearson reports Consultancy: Janssen.

Aung M. Tun reports Consultancy: ADC Therapeutics.

Samuel Yamshon reports Consultancy: Kite Pharma; Advisory Board: Bristol Myers Squibb

Mazyar Shadman reports Consultancy/Ad Hoc Advisory Board: BMS, AbbVie, Adaptive Biotechnologies, AstraZeneca, Beigene, Genentech, Gilead, Incyte, Janssen, Lilly, Merck, TG Therapeutics; Research Funding: Genentech, AstraZeneca, BeiGene, BMS, TG Therapeutics.

Cameron Turtle reports Research Funding: Juno Therapeutics/BMS, Nektar Therapeutics, 10X Genomics, Genscript; Scientific Advisory Boards: Caribou Biosciences, T-CURX, Myeloid Therapeutics, ArsenalBio, Cargo Therapeutics, Celgene/BMS Cell Therapy, Differentia Bio, eGlint; DSMB: Kyverna; Ad hoc advisory roles/consulting: Prescient Therapeutics, Century Therapeutics, Boxer Capital, Novartis, Merck Sharp and Dohme, Abbvie; Stock options: Eureka Therapeutics, Caribou Biosciences, Myeloid Therapeutics, ArsenalBio, Cargo Therapeutics, eGlint; Speaker engagement: Pfizer, Novartis; Patents: CJT is an inventor on patents related to CAR T-cell therapy.

Mehdi Hamadani reports Research Funding: Takeda Pharmaceutical Company, ADC Therapeutics, Spectrum Pharmaceuticals, Astellas Pharma; Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, AbbVie, Caribou, Genmab, Autolus, Forte Biosciences, Byondis, Allovir, Poseida; Speaker’s Bureau: ADC Therapeutics, AstraZeneca, Bei Gene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR.

Alex H. Herrera reports Research funding: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, Pfizer; Consultancy: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, Takeda, Genmab, Pfizer, Abbvie, Allogene Therapeutics

The other authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.. Long-term outcomes after CD19 CAR T-cell therapy categorized by ICI exposure
Cumulative incidence of A) non-relapse mortality and B) relapse. Kaplan-Meier estimates of C) PFS and D) OS. P values per Gray (A-B) or log rank test (C-D). Abbreviations: CAR, chimeric antigen receptor; ICI, immune checkpoint inhibitor; OS, overall survival; PFS, progression-free survival.
Figure 2.
Figure 2.. Univariate regression models for complete response
Estimates from univariate logistic regression models. Abbreviations: CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; HCT, hematopoietic cell transplantation; ICI, immune checkpoint inhibitor; KPS, Karnosfky Performance Status; PR, partial response; axi-cel, axicabtagene ciloleucel; tisa-cel, tisagenlecleucel.
Figure 3.
Figure 3.. Univariate regression models for overall survival
Estimates from Cox regression models. Abbreviations: CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; HCT, hematopoietic cell transplantation; ICI, immune checkpoint inhibitor; KPS, Karnosfky Performance Status; PR, partial response; axi-cel, axicabtagene ciloleucel; tisa-cel, tisagenlecleucel.
Figure 4.
Figure 4.. Univariate regression models for progression-free survival
Estimates from Cox regression models. Abbreviations: CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; HCT, hematopoietic cell transplantation; ICI, immune checkpoint inhibitor; KPS, Karnosfky Performance Status; PR, partial response; axi-cel, axicabtagene ciloleucel; tisa-cel, tisagenlecleucel.
Figure 5.
Figure 5.. Univariate regression models for relapse
Estimates from cause-specific Cox regression models censoring for treatment-related mortality. Abbreviations: CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; HCT, hematopoietic cell transplantation; ICI, immune checkpoint inhibitor; KPS, Karnosfky Performance Status; PR, partial response; axi-cel, axicabtagene ciloleucel; tisa-cel, tisagenlecleucel.
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