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Researchers Identify Significant Risk Factors for Treatment Response to CD-19 CAR-T Therapy in ALL

Results from an analysis presented at the 2019 ASH Annual Meeting reveal significant risk factors for worse treatment response after CD-19 chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).

“[CAR] T-cell therapy targeting CD19 has demonstrated 80-90% complete remission (CR) rate in R/R B-ALL; however, 10% to 20% of patients have no response and the potential etiology and risk factors remain unclear,” explained Xian Zhang, MD, Hebei Yanda Lu Daopei Hospital, Beijing, China, and colleagues.

With an aim to identify factors that may affect the CR rate among these patients, Dr Zhang and colleagues conducted an analysis that included 254 patients with R/R B-ALL. All patients received treatment with a second-generation CD-19 CAR T-cell therapy. The targeted median infused CAR T-cell dose was 3x105/kg.

Next generation sequencing was used for all patients to screen for 58 types of B-ALL-related gene mutations and 49 congenital immune deficiency mutations. Patient and CAR-T product characteristics were analyzed, and chi-squared tests were used to compare CR rates between subgroups.

On day 30, 90.6% of patients achieved CR, 89.4% with minimal residual disease-negative CR. A statistically significant difference in CR rate was observed between female and male patients (84.54% vs 94.27%, respectively; P=.011).

The CR rate for patients who received prior CAR-T or blinatumomab therapy was lower than for those who did not (50% vs 91.53%, respectively; P=.01). The CR rate in patients with MLL-AF4 was 80%, which was lower than those with other or no fusion genes (P=0.041). Additionally, lower CR rate was observed in patients with TP53 mutation than those with other or no mutations (72.73%, 92.11%, and 94.39%, respectively; P=0.004).

Patients with bone marrow blasts >20% had worse outcomes than those with bone marrow blasts ≤ 20% (79.17% vs 97.47%, respectively; P<.001). Receipt of CD28 costimulatory domain was associated with a lower CR rate vs 4-1BB CAR-T products (77.27% vs 91.70%, respectively; P=.053).

“In this analysis, we have observed that significant risk factors for not achieving CR after CD-19 CAR-T therapy include female gender, BM blasts more than 20%, a positive TP53 mutation, treatment with CD28 co-stimulatory domain vs 4-1BB CAR-T product, and mild as opposed to severe CAR-T related neurotoxicity,” Dr Zhang and colleagues concluded. —Janelle Bradley

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