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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]

Although chimeric antigen receptor (CAR) T‐cell therapy has demonstrated remarkable efficacy in patients with chemo‐refractory B‐cell lymphoma, a significant portion is refractory or relapse. Resistance is a major barrier to improving treatment efficacy and long‐term survival in CAR T‐cell therapy, and clinicians have very limited tools to discriminate a priori patients who will or will not respond to treatment. While CD19‐negative relapses due to loss of target antigen is well described, it accounts for only about 30% of cases with treatment failure. Recent efforts have shed light on mechanisms of CD19‐positive relapse due to tumor intrinsic resistance, T‐cell quality/manufacturing, or CAR T‐cell exhaustion mediated by hostile tumor microenvironment. Here, we review the latest updates of preclinical and clinical trials to investigate the mechanisms of resistance and relapse post CAR T‐cell therapy in B cell lymphoma and discuss novel treatment strategies to overcome resistance as well as advances that are useful for a CAR T therapist to optimize and personalize CAR T‐cell therapy. [ABSTRACT FROM AUTHOR]

The future of chimeric antigen receptor T (CAR‐T) therapy remains unclear. New studies are constantly being published confirming the efficacy and favorable safety profile of its innovative enhancements. Currently approved CAR‐T drugs are manufactured exclusively for a specific patient from the recipient's own cells. This does not close the door to further modifications with subsequent personalization and better adaptation to the individual needs. Bringing such a drug to market would involve raising the already high costs, so it is necessary to lower the existing ones. On the other hand, so‐called universal CAR‐T are also getting closer to the patient's bed, but its implementation may struggle with multiple challenges, including development of graft‐versus‐host disease (GvHD) and alloimmunity. However, that off‐the‐shelf therapy could prove useful as a quick solution for patients in very poor condition or excluded from current therapy due to manufacturing limitations. The introduction of currently tested solutions may undoubtedly change the current paradigm of treatment. [ABSTRACT FROM AUTHOR]