CAR T-cell therapy, based on genetically engineered T cells, has demonstrated significant potential in treating hematological malignancies, including B-cell lymphomas. This treatment has a complex lonoutudinal dynamics due to the interplay of different T-cell phenotypes (effector and memory), the expansion of the drug and the cytotoxic effect on both normal and cancerous B-cells, the exhaustion of the immune cells, the tumor immunosupressive environments, and more. Thus, the outcome of the therapy is not yet well understood leading to a variety of responses ranging from sustained complete responses, different types of partial responses, or no response at all. We developed a mechanistic model for the interaction between CAR T- and tumorous B-cells, accounting for the role of the tumor morphology. Simulations showed that tumor lesions with irregular shapes could contribute to treatment variability by increasing their immunosuppressive capabilities impairing CAR T-cell efficacy. This finding is consistent with our analysis of 18F-FDG PET/CT imaging data from 63 relapsed/refractory diffuse large B-cell lymphoma patients receiving CAR T-cells.