Abstract

Tisagenlecleucel's approval in children with B-cell acute lymphoblastic leukemia (B-ALL) was based on the phase 2 ELIANA trial, a global registration study. The ELIANA trial, however, excluded specific subsets of patients facing unique challenges and did not include enough patients to adequately evaluate outcomes in rare sub-populations. Since commercialization of tisagenlecleucel, data has become available that supports therapeutic indications beyond the specific cohorts previously eligible for Chimeric Antigen receptor targeted to CD19 (CD19 CAR) cell therapy on the registration clinical trial. Substantial real-world data and aggregate clinical trial data have addressed gaps in our understanding of response rates, longer-term efficacy, and toxicities associated with CD19 CAR T cells in special populations and rare clinical scenarios. This includes patients with central nervous system-relapsed disease, as they were excluded from ELIANA and other early CAR T cell trials due to concerns about risk of neurotoxicity that have not been born out. There is also interest in the use of CD19 CAR T cells for very high risk patients earlier in the course of therapy, such as patients with persistent minimal residual disease after two cycles of upfront chemotherapy and patients with first relapse of B-ALL. However, these indications are not part of the label for tisagenlecleucel and were historically not included in eligibility criteria for most clinical trials; data addressing these populations is needed. Populations at high risk of relapse, including patients with high-risk cytogenetic lesions, infants with B-ALL, patients with trisomy 21, and young adults with B-ALL may also benefit from earlier treatment with CD19 CAR T cell therapy. It is important to prospectively study patient-reported outcomes given the differential toxicity expected between CD19 CAR T cell therapy and the historic standard of care, hematopoietic cell transplant. Now that CD19 CAR T cell therapy is commercially available, studies evaluating potential access disparities created by this very expensive novel therapy are increasingly pressing.

View details for DOI 10.1016/j.jtct.2023.10.005

View details for PubMedID 37821078