PS939 CAR‐T CELL THERAPY BRIDGING TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION LED TO SUPERIOR SURVIVAL FOR ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS OUT OF REMISSION

Background: In recent decade, CAR‐T cell therapy has surprisingly improved the response rate of refractory and relapsed patients with acute lymphoblastic leukemia (ALL). However, there are still 10∼20% of patients who failed to respond to the treatment, and disease recurrence remains the major concern for patients even achieving remission. Thus, studies focusing on long‐term outcomes are warranted. Aims: To investigate the efficacy and safety of CAR‐T cell therapy in unremission ALL patients, and to explore the role of the strategy of CAR‐T cell bridging to allogeneic hematopoietic cell transplantation (HCT). Methods: A clinical trial was conducted with following inclusion criteria: 1) ALL patients with a disease status out of remission; 2) CD19/CD22 were expressed on leukemic cells; 3) tolerant to intensive treatments. Patients enrolled received preparative treatment of fludarabin and cyclophosphamide, and followed by infusion of CAR‐T cells targeting to CD19/CD22 with a target dose of 5∼10 × 10 6 /kg of recipient weight. HCT procedures were performed after the evaluations, which were at 4 weeks after the CAR‐T cell therapy. Results: In total, 85 patients were enrolled and received CAR‐T cell therapy (details in the table). Complete remission (CR) was attained in 65 patients and partial remission in another 4 patients. Except 4 cases died before evaluation, the CR and overall response rate (ORR) for patients in per protocol set were 80.2% and 85.2% respectively. Among the CR patients, 48 cases were measurable residual disease (MRD) negative, which produced a MRD response of 59.3%. Previous HCT history had a negative impact on the MRD response (P = 0.036). Cytokine‐release syndrome (CRS) was observed in 65 cases (76.5%), but only 27 cases (31.8%) were assessed as grade 3 or higher. Higher blast proportion in marrow was related to increased risk for CRS grade≥2 (P = 0.002). Early death (died in first three months after CAR‐T cell infusion) occurred in 12 patients, who were excluded from the survival analyses. One‐year overall survival (OS) and progression‐free survival (PFS) of the rest 73 cases were 53.4% ± 5.9% and 46.4% ± 5.8% respectively. Twenty‐four cases who received sequential allogeneic HCT had remarkably improved 1‐year OS (79.9% ± 9.2% versus 46.7% ± 7.8%, P  < 0.001) and PFS (73.7% ± 9.3% versus 41.2% ± 7.5%, P  < 0.001) than the ones without HCT (as shown in the figure), although responses to CAR‐T cell therapy was comparable between these two groups of patients. Cox regression results showed allogeneic HCT was a significant impactor for OS (HR 3.606, P = 0.018) as well as PFS (HR 2.901, P = 0.011). Summary/Conclusion: Our data showed, for B‐cell ALL patients out of remission, CAR‐T cell therapy targeting to CD19/CD22 had a promising response but long‐term outcome remained poor. Sequential allogeneic HCT may dramatically improve the OS and PFS, which needs to be further validated by randomized studies.