CAR-T CD19/CD20/CD22/CD30

Study intervention in this clinical trial consisted of 4 cycles of bortezomib-based induction treatment followed stem cell mobilization by cyclophosphamide 3 g/m2...The median PFS and OS of the patients in two groups were all not reached but 21-months PFS was 73% and 55% for two groups respectively (p<0.05); 21-months OS was 100% and 61% for each group (p<0.05) (Figure 1). Conclusion Combined infusion of anti-CD19 and anti-BCMA CART cells after ASCT for high risk MM was safe and effective, and can significantly prolong the PFS and OS compared to single ASCT.

After leukapheresis, all patients received fludarabine-based lymphodepletion chemotherapy with FLAG regimen (Fludarabine 30mg/m2 × 5d, Cytarabine 2g/m2 × 5d and Granulocyte-colony stimulating factor 300ug ×6d) in two cases, FC regimen (Fludarabine 30mg/m2 × 3d and Cyclophosphamide 300mg/m2 × 3d) in five cases, and FC+DAC regimen (Decitabine 50mg × 3d, Fludarabine 30mg/m2 × 3d and Cyclophosphamide 300mg/m2 × 3d) in four cases... Our trial indicates that CAR-T therapy is a safe and powerful salvage approach to R/R AL patients with TP53 alterations and application of decitabine may fuel CAR-T therapy and reduce the relapse rate without increasing therapy related mortality incidences in this high risk population.

After one month from CARTs infusion, some pts were adminstrated IMiDs for maintence therapy after hematopoietic recovery, including oral thalidomide 50mg/d or lenalidomide 10mg/d... Combined sequential administration of CART-19 and CART-BCMA cells can be manufactured from heavily-treated MM pts, and could elicit sustained remission for RRMM pts. Toxicities can be well tolerated. CARTs early expansion and persistence in vivo post infusion may be predictive of clinical outcome.

The tandem CD19/CD22 dual target CAR T cells therapy is a safe and high efficacy treatment for R/R ALL patients. It is possible that multi-targeted CAR-T cell therapy may overcome this resistance mechanism and improve clinical outcomes.