Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 136-144 http://medscipublisher.com/index.php/cge 138 3 Application Status of CAR-T in Major Hematological Malignancies 3.1 Acute lymphoblastic leukemia (ALL): mature application and relapse response CAR-T cell therapy, especially the therapy targeting CD19, has become a mature approach for treating relapsed or refractory B-cell ALL, achieving a high complete remission rate in patients who have no response to conventional treatment (Haslauer et al., 2021; Abbasi et al., 2022; Chen et al., 2022). The approval of CD19-targeted CAR-T therapy by the US Food and Drug Administration is an important breakthrough, bringing new treatment standards and hope for long-term remission to this difficult-to-treat patient group (Holstein and Lunning, 2020; Han et al., 2021; Wang et al., 2023). Despite the remarkable effectiveness, recurrence after CAR-T treatment remains a major problem, usually due to antigen escape or the short survival time of CAR-T cells (Wang et al., 2023). The methods for dealing with recurrence include developing CAR-T cells that can target multiple antigens and adopting combined treatment regimens to enhance the persistence of the therapeutic effect and overcome the problem of drug resistance (Abbasi et al., 2022; Chen et al., 2022). 3.2 Clinical application and effect evaluation of diffuse large B-cell lymphoma CAR-T cell therapy has also shown good effects in the treatment of relapsed or refractory DLBCL. Several products (such as Yescarta, Kymriah, Tecartus) have been approved for clinical use (Wang et al., 2023). Both clinical trials and actual treatment cases have shown that even for patients who have received multiple prior treatments, this therapy can achieve a relatively high objective response rate and complete response rate (Holstein and Lunning, 2020; Han et al., 2021; Haslauer et al., 2021). However, not all patients can achieve long-term remission. Some patients may experience disease recurrence or have serious adverse reactions, such as cytokine release syndrome and neurotoxicity (Wang et al., 2023). Current research is dedicated to optimizing patient screening criteria, improving CAR-T cell design, and exploring combined treatment strategies to enhance the efficacy and safety of DLBCL treatment (Figure 1) (Han et al., 2021; Chen et al., 2022; Zhou et al., 2024). 3.3 Multiple myeloma (MM): new targets and persistent treatment challenges In the field of multiple myeloma treatment, with the development of CAR-T cell therapy targeting B-cell maturation antigen (BCMA), some progress has been made recently, showing positive therapeutic effects in relapsed or refractory cases (Chen et al., 2022). BCMA-targeted CAR-T therapy has achieved a high remission rate, providing a new option for patients with limited treatment options (Holstein and Lunning, 2020; Abbasi et al., 2022; Wang et al., 2023). However, the difficulty in maintaining the therapeutic effect in the long term remains a major problem. Many patients will eventually relapse due to the disappearance of antigens, the short survival time of CAR-T cells, or the immunosuppressive effect of the tumor microenvironment. Current research focuses on finding new therapeutic targets, prolonging the action time of CAR-T cells, and combining CAR-T therapy with other therapies in order to improve the long-term therapeutic effect of MM patients (Holstein and Lunning, 2020; Abbasi et al., 2022; Chen et al., 2022; Zhou et al., 2024). 4 Evaluation of the Efficacy and Safety monitoring of CAR-T Treatment 4.1 Efficacy endpoints: ORR, CR, PFS, OS and monitoring tools The efficacy of CAR-T cell therapy for hematological malignancies was evaluated mainly based on indicators such as overall response rate (ORR), complete response (CR), progression-free survival (PFS), and overall survival (OS) (Roex et al., 2020). For instance, when CAR-T therapy targeting BCMA was used to treat multiple myeloma, the total ORR reached 80.5%, the CR rate was 44.8%, and the median PFS was 12.2 months, which was significantly better than the previous treatment effect (Roex et al., 2020). These indicators are crucial for judging the short-term and long-term effects of treatment in different patients and disease types (Yu and Hua, 2019; Hutton et al., 2019; Xiang et al., 2020).
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