Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 19;6(2):e270015.
doi: 10.1002/jha2.70015. eCollection 2025 Apr.

Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy

Rafael Hernani  1 , Laura Ventura  1 , Begoña Heras  2 , Alicia Serrano  1 , Marcos Rivada  1 , Carolina Martínez-Ciarpaglini  2 , Ana Benzaquén  1 , Blanca Ferrer-Lores  1 , Ariadna Pérez  1 , José Luis Piñana  1 , Juan Carlos Hernández-Boluda  1   3 , Ignacio Arroyo  1 , Paula Amat  1   3 , Irene Pastor-Galán  1 , María José Remigia  1 , Rosa Goterris  1 , Montse Gómez  1 , Anabel Teruel  1   3 , Ana Saus  1 , Consejo Ortí  1 , María José Terol  1   3 , Antonio Ferrández-Izquierdo  2 , Carlos Solano  1   3
Affiliations

Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy

Rafael Hernani et al. EJHaem. .

Abstract

Introduction: Current guidelines do not mandate CD19 tumor expression assessment before chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) patients due to limitations of immunohistochemistry (IHC) or flow cytometry. Quantitative polymerase chain reaction (qPCR) offers a more sensitive alternative for detecting CD19 expression, with the primary advantage that mRNA can be easily extracted from paraffin-embedded tissues.

Methods & results: In our study, we included 51 adult patients with LBCL treated with axicabtagene ciloleucel. Among them, 16 were classified as CD19-negative by IHC; however, qPCR reclassified six (37.5%) as CD19-positive. We then compared the outcomes between consistently CD19-negative (IHC-qPCR-) and CD19-positive (IHC+ and IHC-qPCR+) patients. CD19-negative cohort showed worse 1-year progression-free survival (15 vs. 45%, p = 0.044) and a trend toward shorter duration of response (29 vs. 55%, p = 0.065). Only one (10%) of the CD19-negative patients remained alive and disease-free at last follow-up (6 months), having previously responded to bridge therapy.

Discussion: If confirmed in a large patient cohort, these findings could form the basis for modifying current patient selection criteria. Consistently negative patients may be suboptimal candidates for anti-CD19 CAR-T therapy. Alternative therapeutic options, such as bispecific antibodies or polatuzumab-based regimens, could be considered for this subset of patients.

Keywords: CAR‐T therapy; CD19 tumor expression; large B‐cell lymphoma; quantitative PCR.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(a) Duration of response of the entire cohort. (b) Duration of response according to CD19 lymphoma expression.
FIGURE 2
FIGURE 2
(a) Progression‐free survival of the entire cohort. (b) Progression‐free survival according to CD19 lymphoma expression.
FIGURE 3
FIGURE 3
(a) Overall survival of the entire cohort. (b) Overall survival according to CD19 lymphoma expression.
See this image and copyright information in PMC

References

    1. Jacobson C. A. , Munoz J. , Sun F., et al., “Real‐World Outcomes With Chimeric Antigen Receptor T Cell Therapies in Large B Cell Lymphoma: A Systematic Review and Meta‐Analysis,” Transplant Cell Ther 30 (2024): 77.e1–77.e15. - PubMed
    1. Locke F. L. , Rossi J. M. , Neelapu S. S., et al., “Tumor Burden, Inflammation, and Product Attributes Determine Outcomes of Axicabtagene Ciloleucel in Large B‐cell Lymphoma,” Blood Adv 4 (2020): 4898–4911. - PMC - PubMed
    1. Lownik J. , Boiarsky J. , Birhiray R. , Merchant A. , and Mead M. , “Sequencing of Anti‐CD19 Therapies in the Management of Diffuse Large B‐Cell Lymphoma,” Clinical Cancer Research 30 (2024): 2895–2904. - PMC - PubMed
    1. Spiegel J. Y. , Patel S. , Muffly L., et al., “CAR T Cells With Dual Targeting of CD19 and CD22 in Adult Patients With Recurrent or Refractory B Cell Malignancies: A Phase 1 Trial,” Nature Medicine 27 (2021): 1419–1431. - PMC - PubMed
    1. Plaks V. , Rossi J. M. , Chou J., et al., “CD19 target Evasion as a Mechanism of Relapse in Large B‐cell Lymphoma Treated With Axicabtagene Ciloleucel,” Blood (2021): 1081–1085. - PMC - PubMed

LinkOut - more resources