Bankstown Hospital - Grand Rounds - Further Reading

Welcome to the Grand Rounds Further Reading List, Haematology edition, brought to you by the Clinical Library, on Level 4, next to the Auditorium.

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If you have any questions, please contact the Clinical Library on 9722 8250 or email SWSLHD-BankstownLibrary@health.nsw.gov.au or visit us Monday to Fridays, 8.30am - 5.00pm.

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- CAR-T in SWSLHD"

Karthikeyan, B., et al. (2024). "Cardiotoxic profiles of CAR-T therapy and bispecific T-cell engagers in hematological cancers." Communications Medicine 4(1): 116  https://doi.org/10.1038/s43856-024-00540-9 REQUEST ARTICLE

            Chimeric antigen receptor (CAR) T-cell therapy and bispecific T-cell engagers, which redirect T-cells to tumor antigens, have immensely benefitted patients with relapsed/refractory B-cell cancers. How these therapies differ in cardiotoxicity is underexplored. We used the World Health Organization pharmacovigilance database, VigiBase, to compare cardiotoxicity profiles between CD19-targeted CAR-T therapy and blinatumomab (a CD19/CD3-targeted bispecific T-cell engager).

Lüönd, F., et al. (2025). "DLBCL Cells Emerge after CD19 CAR T Cells with Cross-Antigen Resistance and a Gene Signature Predictive of Clinical CAR T-cell Response." Blood Cancer Discovery 6(6): 580-601  https://doi.org/10.1158/2643-3230.BCD-24-0176 REQUEST ARTICLE

            We demonstrate that DLBCL cells surviving CD19 CAR T-cell treatment develop a resistance phenotype with a “resistance signature” predictive of clinical CAR T-cell response, mediating cross-resistance between CAR T cells targeting different antigens. Our findings suggest that up-front dual-antigen targeting and combination therapies could improve clinical outcomes.

Milunović, V., et al. (2025). "The Improving Outcomes in Relapsed-Refractory Diffuse Large B Cell Lymphoma: The Role of CAR T-Cell Therapy." Current Treatment Options in Oncology 26(6): 445-464  https://doi.org/10.1007/s11864-025-01305-9 REQUEST ARTICLE

            Diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) is the most common aggressive lymphoma and can be cured with CHOP-R immunochemotherapy in 60% of cases. The second-line therapy includes salvage regimens followed by autologous stem cell transplantation (ASCT), which offers a cure to a minority of patients due to limitations in efficacy and eligibility. These data present the unmet need in the field, and this review article focuses on how second-generation chimeric antigen receptor T (CAR T) cell therapy targeting CD19 antigen may improve the outcomes with relapsed/refractory DLBCL. In heavily pretreated patients, who have dismal outcomes with conventional therapy, all three approved products—tisangenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), and lisocabtagene maraleucel (liso-cel) have shown durable, unprecedented complete responses with the potential for cure. When compared to salvage regimens and ASCT as the standard of care, axi-cel and liso-cel, unlike tisa-cel, have demonstrated superiority in long-term control. In ASCT-ineligible r/r DLBCL, liso-cel has shown a favourable benefit-risk ratio. Regarding safety, two adverse events of interest have emerged: cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both of which are manageable. Real-world evidence reflects the results of pivotal trials while favouring axi-cel in heavily pretreated patients, albeit with higher toxicity. The main barrier to the implementation of this treatment modality is the cost associated with the process of CAR T therapy, along with complications and reimbursement issues. However, the barriers can be overcome, and CAR T therapy has the potential to become the standard of care in relapsed/refractory DLBCL. Furthermore, with advances in the scientific engineering of CAR products and the understanding of novel treatment modalities currently being tested in clinical trials, we believe that targeted cellular therapy will become the future of relapsed/refractory DLBCL treatment.

Rampotas, A. and C. Roddie (2025). "The present and future of CAR T-cell therapy for adult B-cell ALL." Blood 145(14): 1485-1497  https://doi.org/10.1182/blood.2023022922   REQUEST ARTICLE

            Chimeric antigen receptor T-cell therapy (CAR-T) targeting CD19 has transformed the management of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), with the US Food and Drug Administration approval of tisagenlecleucel for pediatric/young adult patients and brexucabtagene autoleucel for adults. Efficacy is contingent upon several factors including disease burden. Emerging data suggest that bridging therapy, lymphodepletion, and, for some patients, consolidation therapy have an important role in the success of treatment. Furthermore, strategies to define and manage immunotoxic side effects including hematotoxicity is critical to safe delivery. Advancements in CAR-T design beyond CD19 represent an ongoing therapeutic evolution. Overall, CAR-T signifies a paradigm shift in B-ALL management, with the potential for improved remission and survival in a historically challenging patient population.

Suchiita, A. and S. C. Sonkar (2025). "Revolutionizing immunotherapy: The next frontier in CAR T-cell engineering." Critical Reviews in Oncology/Hematology 211: 104751  https://www.sciencedirect.com/science/article/pii/S1040842825001398 REQUEST ARTICLE

            Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a groundbreaking immunotherapy, offering new hope for cancer treatment, particularly in hematologic malignancies. This review explores the development of CAR T-cell therapy from its first-generation design, which laid the foundational structure, to advanced fifth-generation CARs that integrate sophisticated synthetic biology. Each generation of CARs has introduced critical improvements, such as the incorporation of costimulatory domains, dual signaling pathways, and cytokine release mechanisms to enhance T-cell activation, persistence, and efficacy. Current applications of CAR T-cell therapy have seen significant success in treating cancers like acute lymphoblastic leukemia and diffuse large B-cell lymphoma, with several therapies gaining regulatory approval. However, challenges persist in targeting solid tumors due to the immunosuppressive tumor microenvironment and antigen heterogeneity. Ongoing clinical trials and research are focused on overcoming these barriers through next-generation CAR designs, novel antigen targets, and combination therapies. The review highlights recent advancements, emerging targets, and the potential of CAR T-cell therapy to revolutionize cancer treatment, paving the way for more effective and personalized approaches.

Uslu, U., et al. (2024). "CAR T cell combination therapies to treat cancer." Cancer Cell 42(8): 1319-1325  https://doi.org/10.1016/j.ccell.2024.07.002

REQUEST ARTICLE

            Chimeric antigen receptor (CAR) T cells are effectively used in certain hematological malignancies, though tumor relapse and limited success in solid tumors persist. Recent efforts focus on developing combination treatments to enhance outcomes and safety. Here, we provide a comprehensive overview of such combinatorial approaches and a consideration of ongoing clinical trials.