Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells’ productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.

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Chimeric antigen receptor (CAR) T cell therapy improved the prognosis of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) significantly. Bulky disease and disease stage, as qualitative indicators of the spatial characteristic and distribution status of lymphoma lesions, have not been consistently confirmed to be associated with CAR T cell efficacy. Some researchers have proposed the conception of ‘tumor fragmentation’ and ‘lesion dissemination’, and suggested the association between those indicators and the prognosis of patients receiving chemotherapy. In this study, we reviewed and analysed the PET/CT of patients with DLBCL receiving CAR T cell therapy. We qualitatively described the tumor fragmentation using the tumor volume surface ratio (TVSR), which is the ratio of total metabolic tumor volume to total tumor surface, and we semi-quantitatively described the lesion dissemination using dissemination index (DI), which is the count of lesion invasion sites. We found that lower TVSR or lower DI indicates superior progression-free survival (PFS). Taking these two indicators into account at the same time, patients with lower TVSR and DI have the best prognosis, while patients with higher TVSR and DI have the worst. Overall, the tumor lesion spatial distribution shown in PET/CT before CAR T cell infusion are associated with the prognosis of patients with DLBCL receiving CAR T cell therapy. The lower the degree of tumor fragmentation or the higher the degree of lesion dissemination, the worse the prognosis of patients. They can jointly predict the prognosis.