Key Insights on Hematologic and Lymphatic AEs in CAR-T Therapy

Overview of CAR-T Therapy and Its Adverse Events

Chimeric antigen receptor T-cell (CAR-T) therapy represents a groundbreaking approach in the treatment of hematologic malignancies, particularly in relapsed or refractory cases. This innovative therapy involves the genetic modification of a patient’s T cells to express a CAR that targets specific antigens on cancer cells. While CAR-T therapy has shown remarkable efficacy, leading to significant remission rates in certain hematological cancers, it is not devoid of adverse events (AEs). Notably, hematologic and lymphatic AEs are common, with the FDA Adverse Event Reporting System (FAERS) indicating that approximately 15.2% of CAR-T therapy reports involve these types of AEs, signaling a critical area for clinical focus (Hematologic and lymphatic disorders associated with chimeric antigen receptor T-cell therapy: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database, 2025).

Analysis of Hematologic and Lymphatic AEs in CAR-T Patients

Hematologic AEs, including cytopenias, thrombocytopenia, and B-cell aplasia, are significant complications associated with CAR-T therapy. The incidence varies between products, with anti-CD19 CAR-T therapies reporting higher rates of severe cytopenias compared to anti-BCMA therapies. For example, a comparative analysis revealed that the incidence of hematologic AEs was 13.8% in anti-CD19 CAR-T treatments versus 10.9% in anti-BCMA treatments. This disparity is attributed to the robust T-cell expansion seen with anti-CD19 products, which correlates with a higher incidence of Cytokine Release Syndrome (CRS) (Hematologic and lymphatic disorders associated with chimeric antigen receptor T-cell therapy: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database, 2025).

Table 1: Common Hematologic and Lymphatic AEs in CAR-T Therapy

Impact of Cytokine Release Syndrome on Hematologic AEs

Cytokine Release Syndrome (CRS) is one of the most significant complications arising from CAR-T therapy, associated with increased systemic inflammation and activation of T cells leading to a cascade of cytokines. The severity of CRS directly correlates with the occurrence of hematologic AEs. In patients receiving anti-CD19 CAR-T cells, a higher incidence of grade 3 or higher CRS has been observed, often leading to more pronounced hematologic toxicity. This relationship underscores the need for careful monitoring and management strategies that can mitigate the effects of CRS, thus reducing the severity of hematologic AEs (Hematologic and lymphatic disorders associated with chimeric antigen receptor T-cell therapy: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database, 2025).

Comparative Efficacy of Anti-CD19 vs. Anti-BCMA CAR-T Products

The comparative efficacy of various CAR-T products has drawn considerable attention in recent years. Anti-CD19 CAR-T therapies have historically been the first to gain approval and have demonstrated significant efficacy in treating B-cell malignancies. However, newer anti-BCMA CAR-T therapies are emerging as alternatives with different safety profiles. Studies indicate that patients treated with anti-BCMA CAR-T products exhibit lower incidences of hematologic AEs compared to those receiving anti-CD19 therapies, suggesting an important consideration for patient selection and treatment planning. Moreover, the overall response rate for anti-BCMA therapies has been noted to be higher in certain populations, particularly in multiple myeloma patients (Hematologic and lymphatic disorders associated with chimeric antigen receptor T-cell therapy: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database, 2025).

Table 2: Comparative Efficacy and Safety of CAR-T Products

Clinical Characteristics and Prognostic Factors of AEs in CAR-T Therapy

Understanding the clinical characteristics and prognostic factors associated with AEs in CAR-T therapy is vital for improving patient outcomes. Studies reveal that younger patients, particularly those under 65 years of age, are more likely to experience hematologic and lymphatic AEs. This correlation may be attributed to a more vigorous immune response post-CAR-T infusion in younger individuals. Conversely, older patients tend to face prolonged cytopenias, thereby necessitating a tailored approach to managing treatment-related toxicities based on age and comorbidities (Hematologic and lymphatic disorders associated with chimeric antigen receptor T-cell therapy: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database, 2025).

Table 3: Age-Related Risk Factors for Hematologic AEs

FAQ

What are the most common hematologic AEs associated with CAR-T therapy?

The most common hematologic AEs include neutropenia, thrombocytopenia, cytopenias, and B-cell aplasiThese AEs can significantly affect patient management and treatment protocols.

How does Cytokine Release Syndrome (CRS) impact hematologic AEs?

CRS is associated with heightened systemic inflammation and can exacerbate hematologic AEs through mechanisms such as T-cell activation and cytokine release, leading to increased toxicity.

What distinguishes anti-CD19 and anti-BCMA CAR-T therapies regarding safety and efficacy?

Anti-CD19 CAR-T therapies have higher incidences of hematologic AEs compared to anti-BCMA therapies, which often exhibit more favorable safety profiles while maintaining competitive efficacy in specific patient populations.

How can age influence the risk of AEs in CAR-T therapy?

Younger patients tend to experience more frequent and severe hematologic AEs due to their robust immune responses, while older patients may face prolonged cytopenias, indicating the need for age-adjusted treatment strategies.

Are there strategies to mitigate hematologic AEs in CAR-T therapy?

Implementing supportive care measures, careful patient selection, and monitoring for early signs of AEs can help manage the risks associated with hematologic toxicities following CAR-T therapy.

References

1. Hematologic and lymphatic disorders associated with chimeric antigen receptor T-cell therapy: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database. Retrieved from https://doi.org/10.1186/s12885-025-14227-4

2. Prognostic significance of baseline serum ferritin in newly diagnosed multiple myeloma cases: A retrospective study from southern India. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12066130/

3. Innovative evaluation of selinexor and JQ1 synergy in leukemia therapy via C-MYC inhibition. Retrieved from https://doi.org/10.1186/s12967-025-06525-z

4. Defining the Molecular Intricacies of Human Papillomavirus-Associated Tonsillar Carcinoma. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12062609/

5. Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens. Retrieved from https://doi.org/10.1038/s43018-023-00657-1

6. Identification and construction of a novel NET-related gene signature for predicting prognosis in multiple myeloma. Retrieved from https://doi.org/10.1007/s10238-025-01692-1

7. Research progress on the mechanism of tumor cell ferroptosis regulation by epigenetics