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The rise of immuno‐oncology, including the use of chimeric antigen receptor T‐cell (CAR‐T) therapy is bringing in a new wave of cancer treatments, particularly in hematologic malignancies. However, data on their adverse events, particularly of the eye, is under‐reported. To assess the ocular adverse events associated with the six FDA‐approved CAR‐T cell therapies, a disproportionality analysis utilizing the FAERS database was conducted from the first quarter of 2017 to the third quarter of 2023, as well as a systematic review of case reports of ocular events following CAR‐T cell therapy up to December 20, 2023. A total of 53 ocular adverse events were identified from the FDAs FAERS database. The adverse events most frequently observed were mydriasis and xerophthalmia with tisagenlecleucel (Kymriah). The systematic review resulted in 8 case reports encompassing 19 patients which included a total of 27 events. This study demonstrates the importance of anticipation of potential ocular adverse events by ophthalmologists and oncologists as they can greatly contribute to morbidity in patients with cancer. [ABSTRACT FROM AUTHOR]

Background: While chimeric antigen receptor (CAR) T‐cell therapy has revolutionized the treatment outcomes of relapsed/refractory hematological malignancies, this therapy is associated with post‐treatment cytopenias, which can pose a challenge to its safe administration. This study describes the management of post‐CAR T cytopenias using the thrombopoietin mimetic eltrombopag. Methods: This retrospective analysis included adult patients with lymphoma or myeloma who received CAR T‐cell therapy at two academic medical centers. Eltrombopag was initiated for patients who had persistent high‐grade leukopenia and/or thrombocytopenia beyond 21 days post‐CAR T infusion. Risk factors and outcomes were assessed and compared for patients who did or did not receive eltrombopag. Results: Among the 185 patients analyzed, a majority (88%) experienced thrombocytopenia or leukopenia at day +30 post‐CAR T infusion. A total of 42 patients met the criteria for eltrombopag treatment and initiated therapy. Patients who received eltrombopag were more likely to have pre‐existing cytopenias at lymphodepletion, receive bridging therapy, experience an infection, or require intensive care. Recovery from cytopenias occurred within 180 days for a majority (94%) of patients. Conclusions: The use of eltrombopag for post‐CAR T leukopenia and thrombocytopenia was considered safe without any significant toxicities. The use of eltrombopag for post‐CAR T cytopenias might be effective in a high‐risk patient population but requires further study. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T‐cell (CAR‐T) therapy has demonstrated unprecedented success in the treatment of various hematologic malignancies including relapsed or refractory (R/R) B‐cell acute lymphoblastic leukemia (B‐ALL). Currently, there are two FDA‐approved CD19‐directed CAR‐T cell products for the treatment of adults with R/R B‐ALL. Despite high remission rates following CD19 CAR‐T cell therapy in R/R B‐ALL, remission durability remains limited in most adult patients, with relapse observed frequently in the absence of additional consolidation therapy. Furthermore, the burden of CAR‐T cell toxicity remains significant in adults with R/R B‐ALL and further limits the wide utilization of this effective therapy. In this review, we discuss patient and disease factors that are linked to CAR‐T cell therapy outcomes in R/R B‐ALL and strategies to optimize durability of response to reduce relapse and mitigate toxicity in the adult population. We additionally discuss future approaches being explored to maximize the benefit of CAR‐T in adults with B‐ALL. [ABSTRACT FROM AUTHOR]

Chimeric receptor antigen T cell (CAR‐T cell) therapy has demonstrated effectiveness and therapeutic potential in the immunotherapy of hematological malignancies, representing a promising breakthrough in cancer treatment. Despite the efficacy of CAR‐T cell therapy in B‐cell lymphoma, response variability, resistance, and side effects remain persistent challenges. The tumor microenvironment (TME) plays an intricate role in CAR‐T cell therapy of B‐cell lymphoma. The TME is a complex and dynamic environment that includes various cell types, cytokines, and extracellular matrix components, all of which can influence CAR‐T cell function and behavior. This review discusses the design principles of CAR‐T cells, TME in B‐cell lymphoma, and the mechanisms by which TME influences CAR‐T cell function. We discuss emerging strategies aimed at modulating the TME, targeting immunosuppressive cells, overcoming inhibitory signaling, and improving CAR‐T cell infiltration and persistence. Therefore, these processes enhance the efficacy of CAR‐T cell therapy and improve patient outcomes in B‐cell lymphoma. Further research will be needed to investigate the molecular and cellular events that occur post‐infusion, including changes in TME composition, immune cell interactions, cytokine signaling, and potential resistance mechanisms. Understanding these processes will contribute to the development of more effective CAR‐T cell therapies and strategies to mitigate treatment‐related toxicities. [ABSTRACT FROM AUTHOR]

The success of chimeric antigen receptor T‐cell (CAR‐T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer in a truly personalized fashion. Second generation chimeric antigen receptors (CAR) incorporating co‐stimulatory molecules like 4‐1BB or CD28 were able to overcome some of the hindrances with initial CAR constructs resulting in efficacious products. Many second‐generation CAR‐T products have been approved in the treatment of relapsed/refractory hematologic malignancies including multiple myeloma (MM), non‐Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia. However, challenges remain in optimizing the manufacturing, timely access, limiting the toxicity from CAR‐T infusions and improving sustainability of responses derived with CAR‐T therapy. Here, we summarize the clinical trial data leading to approval CAR‐T therapies in MM and NHL, discuss the limitations with current CAR‐T therapy strategies and review emerging strategies for overcoming these limitations. [ABSTRACT FROM AUTHOR]

Objectives: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)‐T cell therapy. Methods: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non‐severe bleeding group. The thromboelastography data was collected on the day of CAR‐T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR‐T cell infusion. Results: The patients of the severe bleeding group had lower platelet (p <.007), maximum amplitude (p =.002), coagulation index (p =.005), and longer coagulation time (p =.019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0–10, opposite on Days 10–20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR‐T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84–0.95; p <.001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35–5.32; p =.006) were significantly associated with high bleeding severity. Conclusions: Thromboelastography was considered to be a good predictor of bleeding severity. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR‐T) therapy has emerged as a revolutionary new pillar in cancer care, particularly in relapsed/refractory (r/r) B‐cell malignancies. Following impressive clinical outcomes in hematological malignancies, the FDA‐approved six CAR‐T cell products for indications such as lymphoma, leukemia, and myeloma. Despite the numerous advantages of CAR‐T cell treatment, several challenges exist that interfere with its therapeutic efficacy. Serious adverse effects connected with the treatment continue to be a major concern. In addition, poor persistence of therapeutics and antigen escape frequently result in tumor relapse. Exorbitant treatment cost further remains a significant barrier to its effective implementation, limiting its accessibility. This review presents progress of CAR‐T research, the key obstacles that hamper promising outcomes for patients with hematological malignancies, and a few strategies to overcome them. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cell therapy has shown great success in treating certain types of hematological malignancies, such as B-cell acute lymphoblastic leukemia (ALL), large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma. However, there are still challenges to overcome, including improving safety, reducing relapses, lowering costs, and addressing barriers in solid tumors. This special issue focuses on the management of CAR-T cell therapy, including apheresis, implementation, toxicities, and long-term survivorship care. The issue also explores optimizations of CAR-T design and biomarkers for predicting toxicities and detecting relapses. [Extracted from the article]