The new hope for pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) boasts an overall survival rate of up to 96%.
The new hope for pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) boasts an overall survival rate of up to 96%.
Recently, CAR-T cell therapy targeting B-cell malignancies has encountered a series of inquiries and challenges, particularly concerning discussions on CAR-T cell-related toxicity, resistance, antigen escape, and limitations in persistence. However, a groundbreaking concept addressing relapse in patients after CAR-T cell therapy has been introduced for the first time: a sequential approach involving distinct targeted CAR-T cell therapies.
Within this approach, CD19 CAR-T cell therapy has demonstrated the ability to achieve complete remission in 60% to 90% of relapsed or refractory acute B-cell lymphoblastic leukemia patients. By experimenting with different combinations and sequential administration strategies of B-cell antigen-targeted CAR-T cell therapies, there’s potential to prevent tumor antigen escape and prolong the persistence of CAR-T cells.
Preliminary clinical trials have provided initial support for this concept, notably a phase II clinical trial aimed at assessing the efficacy of sequential CD19 and CD22 CAR-T cell therapy. Its findings revealed a 79% event-free survival rate, an 80% sustained remission rate, and an impressive 96% overall survival rate among patients receiving targeted doses in sequential therapy. Encouragingly, the overall safety of this sequential therapy appeared manageable, providing long-term survival benefits for children with relapsed or refractory acute B-cell lymphoblastic leukemia.
However, the limitations of antigen escape and limited persistence after CAR-T cell therapy persist. Addressing these challenges, researchers have proposed the hypothesis of sequential administration of CAR-T cell products targeting different antigens, aiming to maintain the persistence of CAR-T cells.
The results of this phase II clinical trial indicate that administering CD22 CAR-T cell therapy following CD19 CAR-T cell infusion can result in longer-lasting remission effects for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia, achieving an 80% sustained remission rate over 18 months and an impressive 96% overall survival rate. Importantly, the overall safety of this sequential therapy is uplifting, providing long-term survival benefits for this specific patient population.
In summary, this study presents groundbreaking evidence for new strategies and directions in CAR-T cell therapy. Despite existing limitations, this therapy demonstrates significant potential in treating uncontrollable acute B-cell lymphoblastic leukemia, potentially offering more enduring treatment effects and long-term survival benefits for these patients. This achievement points towards a viable path for the future development of cell therapies.
This Phase 2 trial, conducted at Beijing GoBroad Boren Hospital in China, enrolled pediatric patients aged 1–18 years diagnosed with relapsed or refractory B-cell acute lymphocytic leukaemia (ALL) showing CD19 and CD22 positivity exceeding 95%.
