Table 2. Lessons learned from ELIANA trial and future directions of CAR T-cell therapy.

Issues learned from this study

Tisagenlecleucel is effective in pediatric and young adults with relapsed/refractory B-ALL

No reported relapses after HSCT with limited number of follow-up (n=8) and some patients can be cured with tisagenlecleucel treatment only

Although majority of relapses occurred within 12 months after tisagenlecleucel infusion, 6 of 24 (25%) relapses occurred at >12 months

Loss of target antigen (CD19) and loss of CAR T-cell persistence and/or B-cell aplasia are the major mechanisms of relapse

Cytokine release syndrome and neurologic events are commonly seen within 8 weeks of infusion

No new severe adverse effects in long-term, mostly happening within 8 weeks after infusion

B-cell aplasia can persist for a long time, which duration is associated with remission, and hypogammaglobulinemia and infections are seen

Evaluation of health-related quality of life shows continuous improvement

Future directions

Development of CAR T-cells that target multiple antigens (e.g., CD19 and 22) or co-administration of multiple CAR T-cells

Devise the CAR T-cells with prolonged persistence: co-stimulatory molecule, humanized molecule, epigenetic alternation

Optimal lymphodepleting chemotherapy (e.g., exposure to fludarabine)

Confirmation of efficacy in the extramedullary disease (e.g., central nervous system, testis)

Establishment of risk criteria after CAR T-cell therapy (e.g., next-generation sequencing MRD, monitoring of B-cell aplasia) for subsequent therapy

CAR, chimeric antigen receptor; ALL, acute lymphoblastic leukemia; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease.