How does the disease burden affect the efficacy of CAR-T cell therapy

During the annual meeting of the American Association for Cancer Research (AACR), the CT078 test results showed that the majority of adult patients with recurrent B cell acute lymphoblastic leukemia achieved complete remission after 19–28z CAR-T cells treatment, and patients with low disease burden achieved more lasting remission.

The study showed that after first-line chemotherapy for minimal residual disease (MRD), 19–28z CAR-T cell therapy can maximize the remission and survival of patients, and makes it possible to avoid hematopoietic stem cell transplantation (HSCT) on high-risk patients.

The prognosis of relapsed / refractory ALL is very poor. In order to explore a more effective treatment, researchers had a CD19 CAR-T evaluation for the therapy efficacy on these patients. The results showed that this treatment had high reaction rate on recurrent B-ALL patients.

In this study, 51 patients received 19–28z CAR-T cells. Before the infusion of T cells, the researchers assessed the disease burden by bone marrow biopsy. The patients were divided into two groups: MRD (bone marrow progenitor cells were less than 5%) and morphological group (bone marrow progenitor cells were more than 5%).

Results showed that the complete remission rate of MRD group was 95%, and the morphological group 77%. While for the the patients achieving complete remission in MRD group, the median free-event survival was not reached, and morphological group was 6.3 months; median overall survival was also not reached, and morphological group was 17 months, which showed that survival benefit of MRD group is obviously better than that of morphological group.

Then the stem cell transplantation on the prognosis of the two groups of patients did not made an affect. How the significance of HSCT in the end needed more patients and longer accurate assessment. In addition, the results of the study also raised a question — at least for some patients, can the 19–28z CAR-T cell therapy be taken as a clear treatment rather than a bridging therapy after stem cell transplantation?

Safety analysis showed that the MRD group had mild adverse reactions. Two main CAR-T designed cell related adverse reactions were cytokine release syndrome and neurotoxicity: the incidence of group MRD were 5% and 15%, while the morphology group were 42% and 58%.